dbSNP rs572116498: GYPA:p.Arg115Cys (chr4-144116868-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002099.8(GYPA):c.343C>T(p.Arg115Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 1,588,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000077 ( 0 hom. )

Consequence

GYPA
NM_002099.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.76

Variant links:

Genes affected

GYPA (HGNC:4702): (glycophorin A (MNS blood group)) Glycophorins A (GYPA) and B (GYPB) are major sialoglycoproteins of the human erythrocyte membrane which bear the antigenic determinants for the MN and Ss blood groups. In addition to the M or N and S or s antigens that commonly occur in all populations, about 40 related variant phenotypes have been identified. These variants include all the variants of the Miltenberger complex and several isoforms of Sta, as well as Dantu, Sat, He, Mg, and deletion variants Ena, S-s-U- and Mk. Most of the variants are the result of gene recombinations between GYPA and GYPB. [provided by RefSeq, Jul 2008]

GYPA links:

ENSG00000285783 (HGNC:):

ENSG00000285783 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06257388).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GYPA	NM_002099.8 link	c.343C>T	p.Arg115Cys	missense_variant	Exon 5 of 7	ENST00000641688.3	NP_002090.4	P02724A0A0C4DFT7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GYPA	ENST00000641688.3 link	c.343C>T	p.Arg115Cys	missense_variant	Exon 5 of 7		NM_002099.8	ENSP00000493142.2		A0A0C4DFT7

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

251000

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135640

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000766

AC:

AN:

1435860

Hom.:

Cov.:

AF XY:

0.00000977

AC XY:

AN XY:

716216

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000551

Gnomad4 OTH exome

AF:

0.0000336

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000386

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.022

DANN

Benign

0.89

DEOGEN2

Benign

0.081

.;T;T;.;.;.;.;.;.;T;T;.;.;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.2

FATHMM_MKL

Benign

0.0029

LIST_S2

Benign

0.78

T;.;T;T;T;.;.;T;T;T;T;T;T;T

M_CAP

Benign

0.0067

MetaRNN

Benign

0.063

T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.58

PrimateAI

Benign

0.22

PROVEAN

Uncertain

-3.5

.;.;D;.;D;.;.;.;.;.;D;D;D;D

REVEL

Benign

0.071

Sift

Benign

0.079

.;.;T;.;T;.;.;.;.;.;T;D;T;D

Sift4G

Benign

0.068

T;.;T;.;T;.;T;.;.;.;T;T;T;T

Polyphen

1.0

.;.;.;.;.;.;.;.;.;.;D;D;D;.

Vest4

0.21

MutPred

0.47

.;Loss of MoRF binding (P = 0.0079);Loss of MoRF binding (P = 0.0079);Loss of MoRF binding (P = 0.0079);.;.;.;.;.;.;.;.;.;.;

MVP

0.030

MPC

0.022

ClinPred

0.45

GERP RS

-9.6

gMVP

0.032

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over