chr13-94331956-T-C

Position:

• chr13-94331956-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005708.5(GPC6):​c.1152+25833T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 152,298 control chromosomes in the GnomAD database, including 222 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 0.045 (222 hom., cov: 32)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.518

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPC6	NM_005708.5	c.1152+25833T>C		intron_variant		ENST00000377047.9	NP_005699.1
GPC6	XM_017020300.2	c.942+25833T>C		intron_variant			XP_016875789.1
GPC6	XM_047429990.1	c.942+25833T>C		intron_variant			XP_047285946.1
GPC6	XM_017020302.2	c.459+25833T>C		intron_variant			XP_016875791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPC6	ENST00000377047.9	c.1152+25833T>C		intron_variant		1	NM_005708.5	ENSP00000366246.3

Frequencies

GnomAD3 genomes AF: 0.0449 AC: 6836 AN: 152180 Hom.: 222 Cov.: 32

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0512

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.0946

Gnomad SAS AF: 0.0188

Gnomad FIN AF: 0.0278

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0646

Gnomad OTH AF: 0.0382

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

GnomAD4 genome AF: 0.0449 AC: 6841 AN: 152298 Hom.: 222 Cov.: 32 AF XY: 0.0445 AC XY: 3314 AN XY: 74464

Gnomad4 AFR AF: 0.0117

Gnomad4 AMR AF: 0.0510

Gnomad4 ASJ AF: 0.0231

Gnomad4 EAS AF: 0.0945

Gnomad4 SAS AF: 0.0188

Gnomad4 FIN AF: 0.0278

Gnomad4 NFE AF: 0.0646

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0551 Hom.: 252

Bravo AF: 0.0460

Asia WGS AF: 0.0610 AC: 211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.5
DANN	Benign	0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs17196161; hg19: chr13-94984210;