13-91693325-C-T

Position:

• chr13-91693325-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004466.6(GPC5):​c.464C>T​(p.Ala155Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,613,624 control chromosomes in the GnomAD database, including 13,465 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.14 (1732 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11733 hom.)
• Consequence: GPC5 NM_004466.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.79

Genes affected

GPC5 (HGNC:4453): (glypican 5) Cell surface heparan sulfate proteoglycans are composed of a membrane-associated protein core substituted with a variable number of heparan sulfate chains. Members of the glypican-related integral membrane proteoglycan family (GRIPS) contain a core protein anchored to the cytoplasmic membrane via a glycosyl phosphatidylinositol linkage. These proteins may play a role in the control of cell division and growth regulation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016306639).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPC5	NM_004466.6	c.464C>T	p.Ala155Val	missense_variant	3/8	ENST00000377067.9	NP_004457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPC5	ENST00000377067.9	c.464C>T	p.Ala155Val	missense_variant	3/8	1	NM_004466.6	ENSP00000366267	P1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21530 AN: 151874 Hom.: 1728 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.0931

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.162

GnomAD3 exomes AF: 0.138 AC: 34770 AN: 251324 Hom.: 2853 AF XY: 0.141 AC XY: 19142 AN XY: 135830

Gnomad AFR exome AF: 0.186

Gnomad AMR exome AF: 0.117

Gnomad ASJ exome AF: 0.133

Gnomad EAS exome AF: 0.293

Gnomad SAS exome AF: 0.180

Gnomad FIN exome AF: 0.0841

Gnomad NFE exome AF: 0.113

Gnomad OTH exome AF: 0.141

GnomAD4 exome AF: 0.119 AC: 174344 AN: 1461632 Hom.: 11733 Cov.: 33 AF XY: 0.121 AC XY: 87896 AN XY: 727150

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.119

Gnomad4 ASJ exome AF: 0.132

Gnomad4 EAS exome AF: 0.292

Gnomad4 SAS exome AF: 0.181

Gnomad4 FIN exome AF: 0.0794

Gnomad4 NFE exome AF: 0.107

Gnomad4 OTH exome AF: 0.131

GnomAD4 genome AF: 0.142 AC: 21573 AN: 151992 Hom.: 1732 Cov.: 32 AF XY: 0.144 AC XY: 10704 AN XY: 74276

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.291

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.0931

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.161

Alfa AF: 0.120 Hom.: 3074

Bravo AF: 0.148

TwinsUK AF: 0.110 AC: 409

ALSPAC AF: 0.119 AC: 457

ESP6500AA AF: 0.187 AC: 822

ESP6500EA AF: 0.113 AC: 970

ExAC AF: 0.140 AC: 17019

Asia WGS AF: 0.203 AC: 710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T;.
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.63	T;T
MetaRNN	Benign	0.0016	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.
MutationTaster	Benign	0.064	P
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.8	D;.
REVEL	Benign	0.084
Sift	Benign	0.032	D;.
Sift4G	Uncertain	0.048	D;T
Polyphen		0.013	B;.
Vest4		0.043
MPC		0.034
ClinPred		0.026	T
GERP RS		4.2
Varity_R		0.11
gMVP		0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs553717; hg19: chr13-92345579; COSMIC: COSV65586039;