rs9584093

Variant names:

• chr13-93224531-T-C
• rs9584093
• XM_047429990.1:c.-2202T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047429990.1(GPC6):​c.-2202T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,172 control chromosomes in the GnomAD database, including 3,041 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 0.20 (3041 hom., cov: 32)
• Consequence: GPC6 XM_047429990.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.559
• Publications: 5 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=-0.73).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC6	XM_047429990.1	c.-2202T>C		5_prime_UTR_variant	Exon 1 of 9		XP_047285946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000302670	ENST00000788637.1	n.370+4149T>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30104 AN: 152054 Hom.: 3043 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.198 AC: 30101 AN: 152172 Hom.: 3041 Cov.: 32 AF XY: 0.198 AC XY: 14767 AN XY: 74400

African (AFR) AF: 0.161 AC: 6699 AN: 41516

American (AMR) AF: 0.246 AC: 3766 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 712 AN: 3466

East Asian (EAS) AF: 0.304 AC: 1572 AN: 5166

South Asian (SAS) AF: 0.218 AC: 1053 AN: 4826

European-Finnish (FIN) AF: 0.184 AC: 1952 AN: 10606

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13751 AN: 67994

Other (OTH) AF: 0.210 AC: 442 AN: 2106

Alfa AF: 0.204 Hom.: 10233

Bravo AF: 0.203

Asia WGS AF: 0.243 AC: 847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.42
DANN	Benign	0.61
PhyloP100		-0.56

Splicing

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

Other links and lift over

dbSNP: rs9584093; hg19: chr13-93876784; COSMIC: COSV107488516;