13-93260737-C-T

Variant names:

• chr13-93260737-C-T
• rs1328369
• NM_005708.5:c.160+33121C>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.160+33121C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 151,818 control chromosomes in the GnomAD database, including 25,071 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 0.57 (25071 hom., cov: 31)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.552
• Publications: 3 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

ENSG00000302670 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC6	NM_005708.5	c.160+33121C>T		intron_variant	Intron 1 of 8	ENST00000377047.9	NP_005699.1
GPC6	XM_047429990.1	c.-51+34055C>T		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+33121C>T		intron_variant	Intron 1 of 8	1	NM_005708.5	ENSP00000366246.3
ENSG00000302670	ENST00000788637.1	n.370+40355C>T		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86171 AN: 151700 Hom.: 25029 Cov.: 31

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.560

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

GnomAD4 genome AF: 0.568 AC: 86271 AN: 151818 Hom.: 25071 Cov.: 31 AF XY: 0.565 AC XY: 41947 AN XY: 74200

African (AFR) AF: 0.659 AC: 27260 AN: 41388

American (AMR) AF: 0.663 AC: 10108 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1674 AN: 3464

East Asian (EAS) AF: 0.670 AC: 3458 AN: 5158

South Asian (SAS) AF: 0.546 AC: 2630 AN: 4820

European-Finnish (FIN) AF: 0.447 AC: 4704 AN: 10526

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.514 AC: 34885 AN: 67896

Other (OTH) AF: 0.564 AC: 1189 AN: 2108

Alfa AF: 0.529 Hom.: 26426

Bravo AF: 0.593

Asia WGS AF: 0.611 AC: 2122 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.33
DANN	Benign	0.59
PhyloP100		-0.55
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: rs1328369; hg19: chr13-93912990;