Variant chr2-126656286-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002101.5(GYPC):c.23A>G(p.Asn8Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000836 in 1,602,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Affects (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000087 ( 0 hom. )

Consequence

GYPC
NM_002101.5 missense

Scores

Clinical Significance

Affects no assertion criteria provided O:1

Conservation

PhyloP100: -0.808

Variant links:

Genes affected

GYPC (HGNC:4704): (glycophorin C (Gerbich blood group)) Glycophorin C (GYPC) is an integral membrane glycoprotein. It is a minor species carried by human erythrocytes, but plays an important role in regulating the mechanical stability of red cells. A number of glycophorin C mutations have been described. The Gerbich and Yus phenotypes are due to deletion of exon 3 and 2, respectively. The Webb and Duch antigens, also known as glycophorin D, result from single point mutations of the glycophorin C gene. The glycophorin C protein has very little homology with glycophorins A and B. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

GYPC links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27856404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GYPC	NM_002101.5 linkuse as main transcript	c.23A>G	p.Asn8Ser	missense_variant	1/4	ENST00000259254.9	NP_002092.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GYPC	ENST00000259254.9 linkuse as main transcript	c.23A>G	p.Asn8Ser	missense_variant	1/4	1	NM_002101.5	ENSP00000259254	P2	P04921-1

Frequencies

GnomAD3 genomes

AF:

0.0000527

AC:

AN:

151798

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000314

AC:

AN:

222748

Hom.:

AF XY:

0.0000326

AC XY:

AN XY:

122624

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000622

Gnomad OTH exome

AF:

0.000181

GnomAD4 exome

AF:

0.0000869

AC:

126

AN:

1450326

Hom.:

Cov.:

AF XY:

0.0000777

AC XY:

AN XY:

720900

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000112

Gnomad4 OTH exome

AF:

0.0000335

GnomAD4 genome

AF:

0.0000527

AC:

AN:

151798

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74130

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000250

AC:

ClinVar

Significance: Affects

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Blood group, Gerbich system

Other:1

Affects, no assertion criteria provided

literature only

OMIM

May 01, 1991

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.69

CADD

Benign

3.3

DANN

Benign

0.82

DEOGEN2

Benign

0.014

T;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.33

T;T

M_CAP

Benign

0.0088

MetaRNN

Benign

0.28

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

6.5e-9

A;A;A

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.91

N;N

REVEL

Benign

0.084

Sift

Uncertain

0.0070

D;T

Sift4G

Benign

0.098

T;T

Polyphen

0.78

P;.

Vest4

0.23

MutPred

0.073

Gain of phosphorylation at N8 (P = 0.0127);Gain of phosphorylation at N8 (P = 0.0127);

MVP

0.081

MPC

0.0055

ClinPred

0.039

GERP RS

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.034

gMVP

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over