13-93756253-A-G

Variant names:

• chr13-93756253-A-G
• rs7995215
• NM_005708.5:c.320-73901A>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.320-73901A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 151,948 control chromosomes in the GnomAD database, including 36,264 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 0.68 (36264 hom., cov: 32)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 22 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.835 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.320-73901A>G		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.320-73901A>G		intron	N/A	ENSP00000366246.3

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103134 AN: 151830 Hom.: 36200 Cov.: 32

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.726

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.680 AC: 103262 AN: 151948 Hom.: 36264 Cov.: 32 AF XY: 0.684 AC XY: 50789 AN XY: 74208

African (AFR) AF: 0.843 AC: 34945 AN: 41458

American (AMR) AF: 0.726 AC: 11070 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1845 AN: 3472

East Asian (EAS) AF: 0.773 AC: 3977 AN: 5146

South Asian (SAS) AF: 0.674 AC: 3242 AN: 4812

European-Finnish (FIN) AF: 0.640 AC: 6758 AN: 10560

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39358 AN: 67938

Other (OTH) AF: 0.664 AC: 1403 AN: 2112

Alfa AF: 0.623 Hom.: 74857

Bravo AF: 0.694

Asia WGS AF: 0.730 AC: 2538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.3
DANN	Benign	0.65
PhyloP100		-1.2
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: rs7995215; hg19: chr13-94408506;