VCV002505340.1 - ClinVar

NM_001162498.3(LPAR6):c.742A>T (p.Asn248Tyr)

Germline

Classification

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)

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.

Likely pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001162498.3(LPAR6):c.742A>T (p.Asn248Tyr)

Variation ID: 2505340 Accession: VCV002505340.1

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 13q14.2 13: 48411682 (GRCh38) [ NCBI UCSC ] 13: 48985818 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	Jun 17, 2023	Jun 17, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_000321.3:c.1695+30239T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_001162498.3:c.742A>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001155970.1:p.Asn248Tyr	missense
NM_001162497.3:c.742A>T	NP_001155969.1:p.Asn248Tyr	missense
NM_001377316.2:c.742A>T	NP_001364245.1:p.Asn248Tyr	missense
NM_001377317.2:c.742A>T	NP_001364246.1:p.Asn248Tyr	missense
NM_001407165.1:c.1695+30239T>A		intron variant
NM_005767.7:c.742A>T	NP_005758.2:p.Asn248Tyr	missense
NC_000013.11:g.48411682T>A
NC_000013.10:g.48985818T>A
NG_009009.1:g.112936T>A
NG_012874.2:g.37987A>T
NG_127784.1:g.186T>A
LRG_517:g.112936T>A

... more HGVS ... less HGVS

Protein change

N248Y

Other names

Canonical SPDI

NC_000013.11:48411681:T:A

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

VarSome

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
Gene	OMIM	HI score Help 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.
RB1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	3632	3793
LPAR6		-	-	GRCh38 GRCh37	-	144

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.
Hypotrichosis 8	Likely pathogenic (1)	criteria provided, single submitter	-	RCV003234610.1

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.
Likely pathogenic (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: curation	Hypotrichosis 8 Affected status: unknown Allele origin: unknown	SIB Swiss Institute of Bioinformatics Accession: SCV003932428.1 First in ClinVar: Jun 17, 2023 Last updated: Jun 17, 2023	Publications: PubMed (2) PubMed: 19292720‚ 36173926 Comment: This variant is interpreted as likely pathogenic for Hypotrichosis 8, autosomal recessive. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low … (more) This variant is interpreted as likely pathogenic for Hypotrichosis 8, autosomal recessive. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PP1 upgraded to strong); Well-established functional studies show a deleterious effect (PS3 downgraded to supporting); Multiple lines of computational evidence support a deleterious effect on the gene or gene product (PP3). (less)

Comment:

This variant is interpreted as likely pathogenic for Hypotrichosis 8, autosomal recessive. The following ACMG Tag(s) were applied: Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium (PM2); Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (PP1 upgraded to strong); Well-established functional studies show a deleterious effect (PS3 downgraded to supporting); Multiple lines of computational evidence support a deleterious effect on the gene or gene product (PP3).

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:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Cell-trafficking impairment in disease-associated LPA6 missense mutants and a potential pharmacoperone therapy for autosomal recessive woolly hair/hypotrichosis.	Yanagida K	Human molecular genetics	2023	PMID: 36173926
Mutations in the P2RY5 gene underlie autosomal recessive hypotrichosis in 13 Pakistani families.	Tariq M	The British journal of dermatology	2009	PMID: 19292720

Text-mined citations for this variant ...

Record last updated Sep 01, 2024

ClinVar Genomic variation as it relates to human health

NM_001162498.3(LPAR6):c.742A>T (p.Asn248Tyr)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...