NM_005708.5:c.320-141311G>A

Variant names:

• chr13-93688843-G-A
• rs9561428
• NM_005708.5:c.320-141311G>A

Variant summary

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

The NM_005708.5(GPC6):​c.320-141311G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0479 in 151,976 control chromosomes in the GnomAD database, including 357 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 0.048 (357 hom., cov: 32)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539
• 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC6	NM_005708.5	c.320-141311G>A		intron_variant	Intron 2 of 8	ENST00000377047.9	NP_005699.1
GPC6	XM_017020300.2	c.110-141311G>A		intron_variant	Intron 2 of 8		XP_016875789.1
GPC6	XM_047429990.1	c.110-141311G>A		intron_variant	Intron 2 of 8		XP_047285946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPC6	ENST00000377047.9	c.320-141311G>A		intron_variant	Intron 2 of 8	1	NM_005708.5	ENSP00000366246.3

Frequencies

GnomAD3 genomes AF: 0.0479 AC: 7279 AN: 151858 Hom.: 358 Cov.: 32

Gnomad AFR AF: 0.0410

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0556

Gnomad ASJ AF: 0.0943

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.0486

Gnomad FIN AF: 0.0744

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0271

Gnomad OTH AF: 0.0469

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

GnomAD4 genome AF: 0.0479 AC: 7275 AN: 151976 Hom.: 357 Cov.: 32 AF XY: 0.0520 AC XY: 3863 AN XY: 74280

African (AFR) AF: 0.0408 AC: 1696 AN: 41538

American (AMR) AF: 0.0556 AC: 846 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.0943 AC: 327 AN: 3466

East Asian (EAS) AF: 0.274 AC: 1410 AN: 5148

South Asian (SAS) AF: 0.0491 AC: 236 AN: 4808

European-Finnish (FIN) AF: 0.0744 AC: 789 AN: 10598

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0271 AC: 1842 AN: 67876

Other (OTH) AF: 0.0469 AC: 99 AN: 2110

Alfa AF: 0.0392 Hom.: 402

Bravo AF: 0.0510

Asia WGS AF: 0.137 AC: 475 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.57
PhyloP100		-0.54
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: rs9561428; hg19: chr13-94341096;