rs964508

Variant names:

• chr13-93797412-G-C
• rs964508
• NM_005708.5:c.320-32742G>C

Your query was ambiguous. Multiple possible variants found:

• chr13-93797412-G-C
• chr13-93797412-G-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.320-32742G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,074 control chromosomes in the GnomAD database, including 4,755 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 0.24 (4755 hom., cov: 33)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133
• Publications: 0 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005708.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC6	NM_005708.5	MANE Select	c.320-32742G>C		intron	N/A	NP_005699.1	Q9Y625

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC6	ENST00000377047.9	TSL:1 MANE Select	c.320-32742G>C		intron	N/A	ENSP00000366246.3	Q9Y625

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35784 AN: 151956 Hom.: 4751 Cov.: 33

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.235 AC: 35806 AN: 152074 Hom.: 4755 Cov.: 33 AF XY: 0.239 AC XY: 17763 AN XY: 74332

African (AFR) AF: 0.114 AC: 4727 AN: 41498

American (AMR) AF: 0.273 AC: 4174 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 898 AN: 3468

East Asian (EAS) AF: 0.351 AC: 1813 AN: 5160

South Asian (SAS) AF: 0.229 AC: 1106 AN: 4820

European-Finnish (FIN) AF: 0.311 AC: 3284 AN: 10570

Middle Eastern (MID) AF: 0.253 AC: 74 AN: 292

European-Non Finnish (NFE) AF: 0.280 AC: 19016 AN: 67948

Other (OTH) AF: 0.240 AC: 507 AN: 2116

Alfa AF: 0.248 Hom.: 605

Bravo AF: 0.227

Asia WGS AF: 0.245 AC: 854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.29
PhyloP100		-0.13
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: rs964508; hg19: chr13-94449665;