NM_016955.4(SEPSECS):c.114+3A>G AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jan 13, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001281617.13

Allele description

NM_016955.4(SEPSECS):c.114+3A>G

Genes:

LOC129992330:ATAC-STARR-seq lymphoblastoid silent region 15319 [Gene]
SEPSECS:Sep (O-phosphoserine) tRNA:Sec (selenocysteine) tRNA synthase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4p15.2

Genomic location:

Preferred name:

NM_016955.4(SEPSECS):c.114+3A>G

HGVS:

NC_000004.12:g.25160253T>C
NG_028222.1:g.5330A>G
NM_016955.4:c.114+3A>GMANE SELECT
NC_000004.11:g.25161875T>C
NM_016955.3:c.114+3A>G

Links:

Molecular consequence:

NM_016955.4:c.114+3A>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001468946	Laboratoire de Génétique Moléculaire, CHU Bordeaux	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002190740	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 13, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 34234304, 35012964, 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001468946

Laboratoire de Génétique Moléculaire, CHU Bordeaux

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002190740

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 13, 2024)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

High rate of hypomorphic variants as the cause of inherited ataxia and related diseases: study of a cohort of 366 families.

Benkirane M, Marelli C, Guissart C, Roubertie A, Ollagnon E, Choumert A, Fluchère F, Magne FO, Halleb Y, Renaud M, Larrieu L, Baux D, Patat O, Bousquet I, Ravel JM, Cuntz-Shadfar D, Sarret C, Ayrignac X, Rolland A, Morales R, Pointaux M, Lieutard-Haag C, et al.

Genet Med. 2021 Nov;23(11):2160-2170. doi: 10.1038/s41436-021-01250-6. Epub 2021 Jul 7.

PubMed [citation]

PMID:: 34234304

See all PubMed Citations (6)

Details of each submission

From Laboratoire de Génétique Moléculaire, CHU Bordeaux, SCV001468946.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV002190740.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change falls in intron 1 of the SEPSECS gene. It does not directly change the encoded amino acid sequence of the SEPSECS protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs748528138, gnomAD 0.02%). This variant has been observed in individuals with SEPSECS-related conditions (PMID: 34234304, 35012964; Invitae). ClinVar contains an entry for this variant (Variation ID: 984624). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jul 29, 2024

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