The c.4048delG variant, located in coding exon 10 of the MSH6 gene, results from a deletion of one nucleotide at nucleotide position 4048, causing a translational frameshift with a predicted alternate stop codon (p.V1350Sfs*5). This alteration occurs at the 3' terminus of MSH6 gene, is not expected to trigger nonsense-mediated mRNAdecay, and only impacts the last 11 amino acids of the protein. The exact functional effect of this alteration is unknown. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
ClinVar Genomic variation as it relates to human health
NM_000179.3(MSH6):c.4048del (p.Val1350fs)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(1)
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Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Uncertain significance
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000179.3(MSH6):c.4048del (p.Val1350fs)
Variation ID: 1737333 Accession: VCV001737333.2
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 2p16.3 2: 47806825 (GRCh38) [ NCBI UCSC ] 2: 48033964 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Nov 29, 2022 May 1, 2024 Jun 1, 2021 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000179.3:c.4048del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000170.1:p.Val1350fs frameshift NM_001281492.2:c.3658del NP_001268421.1:p.Val1220fs frameshift NM_001281493.2:c.3142del NP_001268422.1:p.Val1048fs frameshift NM_001281494.2:c.3142del NP_001268423.1:p.Val1048fs frameshift NM_001406795.1:c.4144delG NP_001393724.1:p.Val1382Serfs frameshift NM_001406796.1:c.4048delG NP_001393725.1:p.Val1350Serfs frameshift NM_001406797.1:c.3751delG NP_001393726.1:p.Val1251Serfs frameshift NM_001406798.1:c.3874delG NP_001393727.1:p.Val1292Serfs frameshift NM_001406799.1:c.3523delG NP_001393728.1:p.Val1175Serfs frameshift NM_001406800.1:c.*69delG NM_001406801.1:c.*29delG NM_001406802.1:c.*29delG NM_001406803.1:c.3184delG NP_001393732.1:p.Val1062Serfs frameshift NM_001406804.1:c.3970delG NP_001393733.1:p.Val1324Serfs frameshift NM_001406805.1:c.3751delG NP_001393734.1:p.Val1251Serfs frameshift NM_001406806.1:c.3523delG NP_001393735.1:p.Val1175Serfs frameshift NM_001406807.1:c.3523delG NP_001393736.1:p.Val1175Serfs frameshift NM_001406808.1:c.*29delG NM_001406809.1:c.4048delG NP_001393738.1:p.Val1350Serfs frameshift NM_001406811.1:c.3142delG NP_001393740.1:p.Val1048Serfs frameshift NM_001406812.1:c.3142delG NP_001393741.1:p.Val1048Serfs frameshift NM_001406813.1:c.4054delG NP_001393742.1:p.Val1352Serfs frameshift NM_001406814.1:c.3142delG NP_001393743.1:p.Val1048Serfs frameshift NM_001406815.1:c.3142delG NP_001393744.1:p.Val1048Serfs frameshift NM_001406816.1:c.3142delG NP_001393745.1:p.Val1048Serfs frameshift NM_001406817.1:c.2482delG NP_001393746.1:p.Val828Serfs frameshift NM_001406818.1:c.3751delG NP_001393747.1:p.Val1251Serfs frameshift NM_001406819.1:c.3751delG NP_001393748.1:p.Val1251Serfs frameshift NM_001406820.1:c.3751delG NP_001393749.1:p.Val1251Serfs frameshift NM_001406821.1:c.3751delG NP_001393750.1:p.Val1251Serfs frameshift NM_001406822.1:c.*29delG NM_001406823.1:c.3142delG NP_001393752.1:p.Val1048Serfs frameshift NM_001406824.1:c.3751delG NP_001393753.1:p.Val1251Serfs frameshift NM_001406825.1:c.3751delG NP_001393754.1:p.Val1251Serfs frameshift NM_001406826.1:c.3880delG NP_001393755.1:p.Val1294Serfs frameshift NM_001406827.1:c.3751delG NP_001393756.1:p.Val1251Serfs frameshift NM_001406828.1:c.3751delG NP_001393757.1:p.Val1251Serfs frameshift NM_001406829.1:c.3142delG NP_001393758.1:p.Val1048Serfs frameshift NM_001406830.1:c.3751delG NP_001393759.1:p.Val1251Serfs frameshift NM_001406831.1:c.829delG NP_001393760.1:p.Val277Serfs frameshift NM_001406832.1:c.895delG NP_001393761.1:p.Val299Serfs frameshift NM_001407362.1:c.1993delG NP_001394291.1:p.Val665Serfs frameshift NR_176256.1:n.2978delG NR_176257.1:n.4309delG NR_176258.1:n.4238delG NR_176259.1:n.4137delG NR_176260.1:n.2082delG NR_176261.1:n.4019delG NC_000002.12:g.47806825del NC_000002.11:g.48033964del NG_007111.1:g.28679del NG_008397.1:g.103851del LRG_219:g.28679del LRG_219t1:c.4048del LRG_219p1:p.Val1350Serfs - Protein change
- V1220fs, V1350fs, V1048fs
- Other names
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- Canonical SPDI
- NC_000002.12:47806824:G:
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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| HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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| MSH6 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
9161 | 9479 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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| Uncertain significance (1) |
criteria provided, single submitter
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Jun 1, 2021 | RCV002321252.2 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Uncertain significance
(Jun 01, 2021)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002629239.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The c.4048delG variant, located in coding exon 10 of the MSH6 gene, results from a deletion of one nucleotide at nucleotide position 4048, causing a … (more)
The c.4048delG variant, located in coding exon 10 of the MSH6 gene, results from a deletion of one nucleotide at nucleotide position 4048, causing a translational frameshift with a predicted alternate stop codon (p.V1350Sfs*5). This alteration occurs at the 3' terminus of MSH6 gene, is not expected to trigger nonsense-mediated mRNAdecay, and only impacts the last 11 amino acids of the protein. The exact functional effect of this alteration is unknown. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
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Comment:
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
The c.4048delG variant, located in coding exon 10 of the MSH6 gene, results from a deletion of one nucleotide at nucleotide position 4048, causing a translational frameshift with a predicted alternate stop codon (p.V1350Sfs*5). This alteration occurs at the 3' terminus of MSH6 gene, is not expected to trigger nonsense-mediated mRNAdecay, and only impacts the last 11 amino acids of the protein. The exact functional effect of this alteration is unknown. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated May 01, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.