rs9561329

Variant names:

• chr13-93358916-A-G
• rs9561329
• NM_005708.5:c.160+131300A>G

Variant summary

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

The NM_005708.5(GPC6):​c.160+131300A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 150,896 control chromosomes in the GnomAD database, including 2,146 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 0.15 (2146 hom., cov: 31)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.692
• Publications: 6 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 (EAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC6	NM_005708.5	c.160+131300A>G		intron_variant	Intron 1 of 8	ENST00000377047.9	NP_005699.1
GPC6	XM_047429990.1	c.-51+132234A>G		intron_variant	Intron 1 of 8		XP_047285946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPC6	ENST00000377047.9	c.160+131300A>G		intron_variant	Intron 1 of 8	1	NM_005708.5	ENSP00000366246.3

Frequencies

GnomAD3 genomes AF: 0.152 AC: 22996 AN: 150816 Hom.: 2141 Cov.: 31

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.0352

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0949

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.153 AC: 23013 AN: 150896 Hom.: 2146 Cov.: 31 AF XY: 0.158 AC XY: 11674 AN XY: 73662

African (AFR) AF: 0.200 AC: 8230 AN: 41096

American (AMR) AF: 0.227 AC: 3448 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 426 AN: 3460

East Asian (EAS) AF: 0.370 AC: 1885 AN: 5094

South Asian (SAS) AF: 0.119 AC: 565 AN: 4766

European-Finnish (FIN) AF: 0.159 AC: 1622 AN: 10222

Middle Eastern (MID) AF: 0.138 AC: 40 AN: 290

European-Non Finnish (NFE) AF: 0.0949 AC: 6434 AN: 67772

Other (OTH) AF: 0.158 AC: 331 AN: 2092

Alfa AF: 0.122 Hom.: 2785

Bravo AF: 0.163

Asia WGS AF: 0.226 AC: 785 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	4.4
DANN	Benign	0.69
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: rs9561329; hg19: chr13-94011169;