13-93449405-A-T

Variant names:

• chr13-93449405-A-T
• rs4412846
• NM_005708.5:c.161-95858A>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.161-95858A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 152,072 control chromosomes in the GnomAD database, including 27,910 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 0.60 (27910 hom., cov: 32)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.672
• 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

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 (SAS) allele frequency at 95% confidence interval = 0.696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC6	NM_005708.5	c.161-95858A>T		intron_variant	Intron 1 of 8	ENST00000377047.9	NP_005699.1
GPC6	XM_047429990.1	c.-50-95858A>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.161-95858A>T		intron_variant	Intron 1 of 8	1	NM_005708.5	ENSP00000366246.3

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90487 AN: 151954 Hom.: 27903 Cov.: 32

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.641

Gnomad SAS AF: 0.713

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.595 AC: 90529 AN: 152072 Hom.: 27910 Cov.: 32 AF XY: 0.602 AC XY: 44766 AN XY: 74356

African (AFR) AF: 0.420 AC: 17414 AN: 41480

American (AMR) AF: 0.707 AC: 10811 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 2388 AN: 3472

East Asian (EAS) AF: 0.640 AC: 3320 AN: 5184

South Asian (SAS) AF: 0.712 AC: 3426 AN: 4810

European-Finnish (FIN) AF: 0.707 AC: 7475 AN: 10576

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.642 AC: 43596 AN: 67950

Other (OTH) AF: 0.606 AC: 1279 AN: 2112

Alfa AF: 0.517 Hom.: 1665

Bravo AF: 0.587

Asia WGS AF: 0.659 AC: 2295 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	0.57
DANN	Benign	0.46
PhyloP100		-0.67
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: rs4412846; hg19: chr13-94101658;