rs9301951

Variant names:

• chr13-94300578-T-C
• rs9301951
• NM_005708.5:c.1009-5402T>C

Your query was ambiguous. Multiple possible variants found:

• chr13-94300578-T-C
• chr13-94300578-T-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.1009-5402T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0822 in 152,240 control chromosomes in the GnomAD database, including 849 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 0.082 (849 hom., cov: 32)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227
• Publications: 9 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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC6	NM_005708.5	c.1009-5402T>C		intron_variant	Intron 5 of 8	ENST00000377047.9	NP_005699.1
GPC6	XM_017020300.2	c.799-5402T>C		intron_variant	Intron 5 of 8		XP_016875789.1
GPC6	XM_047429990.1	c.799-5402T>C		intron_variant	Intron 5 of 8		XP_047285946.1
GPC6	XM_017020302.2	c.316-5402T>C		intron_variant	Intron 2 of 5		XP_016875791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPC6	ENST00000377047.9	c.1009-5402T>C		intron_variant	Intron 5 of 8	1	NM_005708.5	ENSP00000366246.3

Frequencies

GnomAD3 genomes AF: 0.0821 AC: 12488 AN: 152120 Hom.: 845 Cov.: 32

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.192

Gnomad AMR AF: 0.0525

Gnomad ASJ AF: 0.0691

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.0219

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0371

Gnomad OTH AF: 0.0769

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

GnomAD4 genome AF: 0.0822 AC: 12513 AN: 152240 Hom.: 849 Cov.: 32 AF XY: 0.0797 AC XY: 5933 AN XY: 74422

African (AFR) AF: 0.174 AC: 7225 AN: 41520

American (AMR) AF: 0.0524 AC: 801 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0691 AC: 240 AN: 3472

East Asian (EAS) AF: 0.198 AC: 1022 AN: 5156

South Asian (SAS) AF: 0.0230 AC: 111 AN: 4824

European-Finnish (FIN) AF: 0.0219 AC: 233 AN: 10624

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0371 AC: 2524 AN: 68030

Other (OTH) AF: 0.0784 AC: 166 AN: 2116

Alfa AF: 0.0565 Hom.: 1118

Bravo AF: 0.0917

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.8
DANN	Benign	0.73
PhyloP100		-0.23
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: rs9301951; hg19: chr13-94952832;