rs9524302

Variant names:

• chr13-93989640-C-T
• rs9524302
• NM_005708.5:c.712-38089C>T

Variant summary

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

The NM_005708.5(GPC6):​c.712-38089C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,102 control chromosomes in the GnomAD database, including 1,490 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 0.13 (1490 hom., cov: 32)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.812
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC6	NM_005708.5	c.712-38089C>T		intron_variant	Intron 3 of 8	ENST00000377047.9	NP_005699.1
GPC6	XM_017020300.2	c.502-38089C>T		intron_variant	Intron 3 of 8		XP_016875789.1
GPC6	XM_047429990.1	c.502-38089C>T		intron_variant	Intron 3 of 8		XP_047285946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPC6	ENST00000377047.9	c.712-38089C>T		intron_variant	Intron 3 of 8	1	NM_005708.5	ENSP00000366246.3

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19519 AN: 151982 Hom.: 1486 Cov.: 32

Gnomad AFR AF: 0.0575

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.128 AC: 19533 AN: 152102 Hom.: 1490 Cov.: 32 AF XY: 0.129 AC XY: 9567 AN XY: 74340

African (AFR) AF: 0.0575 AC: 2386 AN: 41518

American (AMR) AF: 0.162 AC: 2469 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 664 AN: 3472

East Asian (EAS) AF: 0.263 AC: 1358 AN: 5154

South Asian (SAS) AF: 0.101 AC: 487 AN: 4824

European-Finnish (FIN) AF: 0.155 AC: 1636 AN: 10574

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10120 AN: 67990

Other (OTH) AF: 0.140 AC: 294 AN: 2100

Alfa AF: 0.141 Hom.: 807

Bravo AF: 0.130

Asia WGS AF: 0.193 AC: 670 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.71
PhyloP100		-0.81
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: rs9524302; hg19: chr13-94641894;