Variant 6-49611034-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_000324.3(RHAG):c.1057G>A(p.Ala353Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000192 in 1,613,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

RHAG
NM_000324.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.332

Variant links:

Genes affected

RHAG (HGNC:10006): (Rh associated glycoprotein) The protein encoded by this gene is erythrocyte-specific and is thought to be part of a membrane channel that transports ammonium and carbon dioxide across the blood cell membrane. The encoded protein appears to interact with Rh blood group antigens and Rh30 polypeptides. Defects in this gene are a cause of regulator type Rh-null hemolytic anemia (RHN), or Rh-deficiency syndrome.[provided by RefSeq, Mar 2009]

RHAG links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008648068).

BP6

Variant 6-49611034-C-T is Benign according to our data. Variant chr6-49611034-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2902956.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RHAG	NM_000324.3 linkuse as main transcript	c.1057G>A	p.Ala353Thr	missense_variant	7/10	ENST00000371175.10	NP_000315.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RHAG	ENST00000371175.10 linkuse as main transcript	c.1057G>A	p.Ala353Thr	missense_variant	7/10	1	NM_000324.3	ENSP00000360217	P2	Q02094-1
RHAG	ENST00000646272.1 linkuse as main transcript	c.1057G>A	p.Ala353Thr	missense_variant	7/10			ENSP00000494337	A2
RHAG	ENST00000646963.1 linkuse as main transcript	c.1057G>A	p.Ala353Thr	missense_variant	7/9			ENSP00000495337
RHAG	ENST00000646939.1 linkuse as main transcript	c.945+1363G>A		intron_variant				ENSP00000494709		Q02094-2

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00349

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000438

AC:

110

AN:

251040

Hom.:

AF XY:

0.000428

AC XY:

AN XY:

135668

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00393

Gnomad NFE exome

AF:

0.0000970

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000180

AC:

263

AN:

1461560

Hom.:

Cov.:

AF XY:

0.000183

AC XY:

133

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00358

Gnomad4 NFE exome

AF:

0.0000432

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000309

AC:

AN:

152266

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00349

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000266

Hom.:

Bravo

AF:

0.0000567

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000420

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Apr 10, 2023

- -

RHAG-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 27, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.73

CADD

Benign

5.2

DANN

Benign

0.078

DEOGEN2

Benign

0.0060

T;.;T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.46

T;T;T;T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.0086

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.48

N;.;.;.;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

1.1

N;.;.;.;.

REVEL

Benign

0.19

Sift

Benign

0.86

T;.;.;.;.

Sift4G

Benign

0.80

T;.;T;T;.

Polyphen

0.0050

B;.;.;.;B

Vest4

0.049

MVP

0.14

MPC

0.26

ClinPred

0.013

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.017

gMVP

0.14

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over