Variant chr4-144119713-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_002099.8(GYPA):c.205A>G(p.Thr69Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,454,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GYPA
NM_002099.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.48

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1

In a glycosylation_site O-linked (GalNAc...) threonine (size 0) in uniprot entity GLPA_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09037474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GYPA	NM_002099.8 linkuse as main transcript	c.205A>G	p.Thr69Ala	missense_variant	3/7	ENST00000641688.3	NP_002090.4
LOC105377460	XR_002959803.2 linkuse as main transcript	n.5270+4484T>C		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.205A>G	p.Thr69Ala	missense_variant	3/7		NM_002099.8	ENSP00000493142	P4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250694

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135514

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1454276

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724044

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 17, 2022

The c.205A>G (p.T69A) alteration is located in exon 3 (coding exon 3) of the GYPA gene. This alteration results from a A to G substitution at nucleotide position 205, causing the threonine (T) at amino acid position 69 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.032

DANN

Benign

0.46

DEOGEN2

Benign

0.032

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

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.48

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

M_CAP

Benign

0.00093

MetaRNN

Benign

0.090

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

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.7

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

REVEL

Benign

0.033

Sift

Benign

0.037

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

Sift4G

Benign

0.11

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

Polyphen

0.0010

.;.;.;.;.;.;.;.;.;B

Vest4

0.056

MutPred

0.52

.;Loss of glycosylation at T69 (P = 0.0071);Loss of glycosylation at T69 (P = 0.0071);Loss of glycosylation at T69 (P = 0.0071);.;.;.;.;.;Loss of glycosylation at T69 (P = 0.0071);

MVP

0.19

MPC

0.020

ClinPred

0.057

GERP RS

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.025

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