13-94331956-T-C

Variant names:

• chr13-94331956-T-C
• rs17196161
• NM_005708.5:c.1152+25833T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.84).
• 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 rank	MANE	Protein	UniProt
GPC6	NM_005708.5	c.1152+25833T>C		intron_variant	Intron 6 of 8	ENST00000377047.9	NP_005699.1
GPC6	XM_017020300.2	c.942+25833T>C		intron_variant	Intron 6 of 8		XP_016875789.1
GPC6	XM_047429990.1	c.942+25833T>C		intron_variant	Intron 6 of 8		XP_047285946.1
GPC6	XM_017020302.2	c.459+25833T>C		intron_variant	Intron 3 of 5		XP_016875791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPC6	ENST00000377047.9	c.1152+25833T>C		intron_variant	Intron 6 of 8	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

African (AFR) AF: 0.0117 AC: 486 AN: 41580

American (AMR) AF: 0.0510 AC: 780 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0231 AC: 80 AN: 3470

East Asian (EAS) AF: 0.0945 AC: 489 AN: 5176

South Asian (SAS) AF: 0.0188 AC: 91 AN: 4830

European-Finnish (FIN) AF: 0.0278 AC: 295 AN: 10624

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0646 AC: 4396 AN: 68004

Other (OTH) AF: 0.0421 AC: 89 AN: 2114

Alfa AF: 0.0531 Hom.: 299

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
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17196161; hg19: chr13-94984210;