13-93641423-A-G

Variant names:

• chr13-93641423-A-G
• rs4085921
• NM_005708.5:c.319+96002A>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.319+96002A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 151,984 control chromosomes in the GnomAD database, including 22,381 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 0.51 (22381 hom., cov: 32)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.862 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+96002A>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.319+96002A>G		intron	N/A	ENSP00000366246.3

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77322 AN: 151864 Hom.: 22320 Cov.: 32

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.883

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.510 AC: 77442 AN: 151984 Hom.: 22381 Cov.: 32 AF XY: 0.514 AC XY: 38153 AN XY: 74262

African (AFR) AF: 0.747 AC: 30981 AN: 41486

American (AMR) AF: 0.536 AC: 8170 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1183 AN: 3460

East Asian (EAS) AF: 0.883 AC: 4553 AN: 5154

South Asian (SAS) AF: 0.518 AC: 2500 AN: 4822

European-Finnish (FIN) AF: 0.399 AC: 4206 AN: 10554

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.360 AC: 24464 AN: 67954

Other (OTH) AF: 0.488 AC: 1028 AN: 2106

Alfa AF: 0.409 Hom.: 44431

Bravo AF: 0.534

Asia WGS AF: 0.698 AC: 2423 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.24
DANN	Benign	0.43
PhyloP100		-1.4
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: rs4085921; hg19: chr13-94293676;