rs761061903

Variant names:

• chr13-93830168-C-G
• rs761061903
• NM_005708.5:c.334C>G

Your query was ambiguous. Multiple possible variants found:

• chr13-93830168-C-G
• chr13-93830168-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_005708.5(GPC6):​c.334C>G​(p.Leu112Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L112F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GPC6 NM_005708.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.70
• 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-AS2 (HGNC:39910): (GPC6 antisense RNA 2)

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.889

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC6	NM_005708.5	MANE Select	c.334C>G	p.Leu112Val	missense	Exon 3 of 9	NP_005699.1	Q9Y625
	GPC6-AS2	NR_046536.1		n.380+648G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC6	ENST00000377047.9	TSL:1 MANE Select	c.334C>G	p.Leu112Val	missense	Exon 3 of 9	ENSP00000366246.3	Q9Y625
	GPC6-AS2	ENST00000445540.1	TSL:5	n.228+648G>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000403 AC: 1 AN: 248122 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000889

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.057	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Uncertain	0.19	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		4.7
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.80
MutPred		0.74		Loss of disorder (P = 0.209)
MVP		0.86
MPC		0.96
ClinPred		0.96	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.62
gMVP		0.74
Mutation Taster		=75/25	polymorphism

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: rs761061903; hg19: chr13-94482421;