NM_005708.5:c.1153-25406G>A

Variant names:

• chr13-94357008-G-A
• rs9524457
• NM_005708.5:c.1153-25406G>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.1153-25406G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,108 control chromosomes in the GnomAD database, including 4,183 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 0.22 (4183 hom., cov: 32)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.426
• Publications: 0 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC6	NM_005708.5	c.1153-25406G>A		intron_variant	Intron 6 of 8	ENST00000377047.9	NP_005699.1
GPC6	XM_017020300.2	c.943-25406G>A		intron_variant	Intron 6 of 8		XP_016875789.1
GPC6	XM_047429990.1	c.943-25406G>A		intron_variant	Intron 6 of 8		XP_047285946.1
GPC6	XM_017020302.2	c.460-25406G>A		intron_variant	Intron 3 of 5		XP_016875791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPC6	ENST00000377047.9	c.1153-25406G>A		intron_variant	Intron 6 of 8	1	NM_005708.5	ENSP00000366246.3

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33578 AN: 151988 Hom.: 4179 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.00367

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.221 AC: 33606 AN: 152108 Hom.: 4183 Cov.: 32 AF XY: 0.217 AC XY: 16113 AN XY: 74342

African (AFR) AF: 0.148 AC: 6156 AN: 41500

American (AMR) AF: 0.304 AC: 4648 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 999 AN: 3468

East Asian (EAS) AF: 0.00367 AC: 19 AN: 5172

South Asian (SAS) AF: 0.110 AC: 528 AN: 4810

European-Finnish (FIN) AF: 0.196 AC: 2077 AN: 10584

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18311 AN: 67972

Other (OTH) AF: 0.271 AC: 571 AN: 2110

Alfa AF: 0.253 Hom.: 9680

Bravo AF: 0.227

Asia WGS AF: 0.0830 AC: 293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.39
DANN	Benign	0.61
PhyloP100		-0.43
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: rs9524457; hg19: chr13-95009262;