13-94238120-T-C

Variant names:

• chr13-94238120-T-C
• rs9516371
• NM_005708.5:c.878-48229T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005708.5(GPC6):​c.878-48229T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 151,946 control chromosomes in the GnomAD database, including 32,565 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.65 (32565 hom., cov: 31)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.689
• Publications: 5 publications found

Genes affected

GPC6 (HGNC:4454): (glypican 6) The glypicans comprise a family of glycosylphosphatidylinositol-anchored heparan sulfate proteoglycans, and they have been implicated in the control of cell growth and cell division. The glypican encoded by this gene is a putative cell surface coreceptor for growth factors, extracellular matrix proteins, proteases and anti-proteases. Mutations in this gene are associated with omodysplasia 1. [provided by RefSeq, Nov 2016]

GPC6 Gene-Disease associations (from GenCC):

• autosomal recessive omodysplasia

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC6	NM_005708.5	c.878-48229T>C		intron_variant	Intron 4 of 8	ENST00000377047.9	NP_005699.1
GPC6	XM_017020300.2	c.668-48229T>C		intron_variant	Intron 4 of 8		XP_016875789.1
GPC6	XM_047429990.1	c.668-48229T>C		intron_variant	Intron 4 of 8		XP_047285946.1
GPC6	XM_017020302.2	c.185-48229T>C		intron_variant	Intron 1 of 5		XP_016875791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPC6	ENST00000377047.9	c.878-48229T>C		intron_variant	Intron 4 of 8	1	NM_005708.5	ENSP00000366246.3

Frequencies

GnomAD3 genomes AF: 0.652 AC: 98951 AN: 151830 Hom.: 32551 Cov.: 31

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.588

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.668

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.652 AC: 99001 AN: 151946 Hom.: 32565 Cov.: 31 AF XY: 0.645 AC XY: 47880 AN XY: 74224

African (AFR) AF: 0.675 AC: 27999 AN: 41452

American (AMR) AF: 0.587 AC: 8969 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2255 AN: 3468

East Asian (EAS) AF: 0.641 AC: 3293 AN: 5140

South Asian (SAS) AF: 0.471 AC: 2262 AN: 4806

European-Finnish (FIN) AF: 0.611 AC: 6436 AN: 10542

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45430 AN: 67950

Other (OTH) AF: 0.667 AC: 1406 AN: 2108

Alfa AF: 0.641 Hom.: 21585

Bravo AF: 0.653

Asia WGS AF: 0.527 AC: 1832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.51
PhyloP100		0.69
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9516371; hg19: chr13-94890374;