Variant rs7658293 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002099.8(GYPA):c.72G>T(p.Glu24Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 999,138 control chromosomes in the GnomAD database, including 74,231 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 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 0.45 ( 11689 hom., cov: 19)

Exomes 𝑓: 0.20 ( 62542 hom. )

Consequence

GYPA
NM_002099.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.682

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:

LOC105377460 (HGNC:):

LOC105377460 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.982088E-4).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GYPA	NM_002099.8 linkuse as main transcript	c.72G>T	p.Glu24Asp	missense_variant	2/7	ENST00000641688.3	NP_002090.4
LOC105377460	XR_002959803.2 linkuse as main transcript	n.5270+5325C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GYPA	ENST00000641688.3 linkuse as main transcript	c.72G>T	p.Glu24Asp	missense_variant	2/7		NM_002099.8	ENSP00000493142	P4

Frequencies

GnomAD3 genomes

AF:

0.451

AC:

47020

AN:

104240

Hom.:

11673

Cov.:

show subpopulations

Gnomad AFR

AF:

0.381

Gnomad AMI

AF:

0.404

Gnomad AMR

AF:

0.481

Gnomad ASJ

AF:

0.489

Gnomad EAS

AF:

0.441

Gnomad SAS

AF:

0.472

Gnomad FIN

AF:

0.533

Gnomad MID

AF:

0.525

Gnomad NFE

AF:

0.475

Gnomad OTH

AF:

0.409

GnomAD3 exomes

AF:

0.129

AC:

20346

AN:

157362

Hom.:

9019

AF XY:

0.119

AC XY:

10109

AN XY:

85064

show subpopulations

Gnomad AFR exome

AF:

0.134

Gnomad AMR exome

AF:

0.240

Gnomad ASJ exome

AF:

0.0861

Gnomad EAS exome

AF:

0.241

Gnomad SAS exome

AF:

0.144

Gnomad FIN exome

AF:

0.0493

Gnomad NFE exome

AF:

0.0934

Gnomad OTH exome

AF:

0.188

GnomAD4 exome

AF:

0.200

AC:

178520

AN:

894792

Hom.:

62542

Cov.:

AF XY:

0.211

AC XY:

94518

AN XY:

446930

show subpopulations

Gnomad4 AFR exome

AF:

0.174

Gnomad4 AMR exome

AF:

0.339

Gnomad4 ASJ exome

AF:

0.301

Gnomad4 EAS exome

AF:

0.425

Gnomad4 SAS exome

AF:

0.431

Gnomad4 FIN exome

AF:

0.468

Gnomad4 NFE exome

AF:

0.148

Gnomad4 OTH exome

AF:

0.259

GnomAD4 genome

AF:

0.451

AC:

47062

AN:

104346

Hom.:

11689

Cov.:

AF XY:

0.451

AC XY:

22417

AN XY:

49752

show subpopulations

Gnomad4 AFR

AF:

0.381

Gnomad4 AMR

AF:

0.482

Gnomad4 ASJ

AF:

0.489

Gnomad4 EAS

AF:

0.441

Gnomad4 SAS

AF:

0.474

Gnomad4 FIN

AF:

0.533

Gnomad4 NFE

AF:

0.475

Gnomad4 OTH

AF:

0.404

Alfa

AF:

0.534

Hom.:

2784

ExAC

AF:

0.0194

AC:

1695

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.77

DANN

Benign

0.42

DEOGEN2

Benign

0.023

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

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00093

LIST_S2

Benign

0.54

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

MetaRNN

Benign

0.00070

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

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

P;P;P;P;P;P;P;P

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.83

.;.;N;.;.;N;N;N

REVEL

Benign

0.026

Sift

Benign

0.45

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

Sift4G

Benign

0.64

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

Polyphen

0.61, 0.010

.;.;.;.;.;P;B;.

Vest4

0.053

MutPred

0.31

.;Loss of glycosylation at T23 (P = 0.0157);Loss of glycosylation at T23 (P = 0.0157);Loss of glycosylation at T23 (P = 0.0157);.;Loss of glycosylation at T23 (P = 0.0157);Loss of glycosylation at T23 (P = 0.0157);Loss of glycosylation at T23 (P = 0.0157);

MPC

0.040

ClinPred

0.0073

GERP RS

-1.8

gMVP

0.018

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over