13-93353552-A-G

Variant names:

• chr13-93353552-A-G
• rs9524017
• NM_005708.5:c.160+125936A>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+125936A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 152,100 control chromosomes in the GnomAD database, including 14,354 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 0.41 (14354 hom., cov: 33)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.575
• Publications: 4 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 = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC6	NM_005708.5	c.160+125936A>G		intron_variant	Intron 1 of 8	ENST00000377047.9	NP_005699.1
GPC6	XM_047429990.1	c.-51+126870A>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+125936A>G		intron_variant	Intron 1 of 8	1	NM_005708.5	ENSP00000366246.3

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62547 AN: 151984 Hom.: 14328 Cov.: 33

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.916

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.404

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.412 AC: 62621 AN: 152100 Hom.: 14354 Cov.: 33 AF XY: 0.418 AC XY: 31047 AN XY: 74350

African (AFR) AF: 0.519 AC: 21549 AN: 41488

American (AMR) AF: 0.464 AC: 7085 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1267 AN: 3466

East Asian (EAS) AF: 0.916 AC: 4740 AN: 5172

South Asian (SAS) AF: 0.471 AC: 2272 AN: 4824

European-Finnish (FIN) AF: 0.314 AC: 3317 AN: 10576

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.308 AC: 20960 AN: 67986

Other (OTH) AF: 0.402 AC: 847 AN: 2108

Alfa AF: 0.355 Hom.: 29075

Bravo AF: 0.433

Asia WGS AF: 0.678 AC: 2354 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	0.25
DANN	Benign	0.30
PhyloP100		-0.57
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: rs9524017; hg19: chr13-94005805;