13-93620709-G-C

Variant names:

• chr13-93620709-G-C
• rs4523817
• NM_005708.5:c.319+75288G>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.319+75288G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 151,902 control chromosomes in the GnomAD database, including 8,879 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 0.34 (8879 hom., cov: 32)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.493
• Publications: 1 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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005708.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC6	NM_005708.5	MANE Select	c.319+75288G>C		intron	N/A	NP_005699.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC6	ENST00000377047.9	TSL:1 MANE Select	c.319+75288G>C		intron	N/A	ENSP00000366246.3

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51258 AN: 151784 Hom.: 8873 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.379

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.338 AC: 51287 AN: 151902 Hom.: 8879 Cov.: 32 AF XY: 0.337 AC XY: 24985 AN XY: 74232

African (AFR) AF: 0.293 AC: 12129 AN: 41422

American (AMR) AF: 0.271 AC: 4130 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.425 AC: 1474 AN: 3466

East Asian (EAS) AF: 0.288 AC: 1486 AN: 5152

South Asian (SAS) AF: 0.239 AC: 1148 AN: 4812

European-Finnish (FIN) AF: 0.379 AC: 3999 AN: 10544

Middle Eastern (MID) AF: 0.342 AC: 100 AN: 292

European-Non Finnish (NFE) AF: 0.378 AC: 25690 AN: 67942

Other (OTH) AF: 0.350 AC: 739 AN: 2110

Alfa AF: 0.361 Hom.: 1257

Bravo AF: 0.327

Asia WGS AF: 0.284 AC: 988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.0
DANN	Benign	0.44
PhyloP100		0.49
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: rs4523817; hg19: chr13-94272962;