NM_005708.5:c.712-33047T>C

Variant names:

• chr13-93994682-T-C
• rs1415736
• NM_005708.5:c.712-33047T>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.712-33047T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.778 in 152,098 control chromosomes in the GnomAD database, including 46,633 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 0.78 (46633 hom., cov: 32)
• Consequence: GPC6 NM_005708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.932
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC6	NM_005708.5	c.712-33047T>C		intron_variant	Intron 3 of 8	ENST00000377047.9	NP_005699.1
GPC6	XM_017020300.2	c.502-33047T>C		intron_variant	Intron 3 of 8		XP_016875789.1
GPC6	XM_047429990.1	c.502-33047T>C		intron_variant	Intron 3 of 8		XP_047285946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPC6	ENST00000377047.9	c.712-33047T>C		intron_variant	Intron 3 of 8	1	NM_005708.5	ENSP00000366246.3

Frequencies

GnomAD3 genomes AF: 0.778 AC: 118302 AN: 151980 Hom.: 46619 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.771

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.845

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.847

Gnomad OTH AF: 0.783

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

GnomAD4 genome AF: 0.778 AC: 118350 AN: 152098 Hom.: 46633 Cov.: 32 AF XY: 0.778 AC XY: 57801 AN XY: 74322

African (AFR) AF: 0.662 AC: 27481 AN: 41486

American (AMR) AF: 0.769 AC: 11737 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 2741 AN: 3470

East Asian (EAS) AF: 0.613 AC: 3149 AN: 5140

South Asian (SAS) AF: 0.822 AC: 3970 AN: 4828

European-Finnish (FIN) AF: 0.845 AC: 8940 AN: 10580

Middle Eastern (MID) AF: 0.827 AC: 243 AN: 294

European-Non Finnish (NFE) AF: 0.847 AC: 57608 AN: 68020

Other (OTH) AF: 0.782 AC: 1652 AN: 2112

Alfa AF: 0.816 Hom.: 37517

Bravo AF: 0.765

Asia WGS AF: 0.702 AC: 2440 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.35
DANN	Benign	0.52
PhyloP100		-0.93
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: rs1415736; hg19: chr13-94646936;