Variant 6-49607203-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000324.3(RHAG):c.1085C>T(p.Ala362Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,228 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

RHAG
NM_000324.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.44

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 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=0.34788334).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RHAG	NM_000324.3 linkuse as main transcript	c.1085C>T	p.Ala362Val	missense_variant	8/10	ENST00000371175.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RHAG	ENST00000371175.10 linkuse as main transcript	c.1085C>T	p.Ala362Val	missense_variant	8/10	1	NM_000324.3	P2	Q02094-1
RHAG	ENST00000646272.1 linkuse as main transcript	c.1085C>T	p.Ala362Val	missense_variant	8/10			A2
RHAG	ENST00000646963.1 linkuse as main transcript	c.1085C>T	p.Ala362Val	missense_variant	8/9
RHAG	ENST00000646939.1 linkuse as main transcript	c.963C>T	p.Gly321=	synonymous_variant	7/9				Q02094-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461228

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726886

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

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

Mar 24, 2023

The c.1085C>T (p.A362V) alteration is located in exon 8 (coding exon 8) of the RHAG gene. This alteration results from a C to T substitution at nucleotide position 1085, causing the alanine (A) at amino acid position 362 to be replaced by a valine (V). 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

0.13

BayesDel_addAF

Benign

-0.025

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.014

T;.;T;T;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.86

D;D;D;D;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.35

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;.;.;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.3

N;.;.;.;.

REVEL

Benign

0.13

Sift

Benign

0.32

T;.;.;.;.

Sift4G

Benign

0.48

T;.;T;T;.

Polyphen

0.11

B;.;.;.;D

Vest4

0.31

MutPred

0.60

Loss of disorder (P = 0.0503);Loss of disorder (P = 0.0503);Loss of disorder (P = 0.0503);Loss of disorder (P = 0.0503);Loss of disorder (P = 0.0503);

MVP

0.32

MPC

0.89

ClinPred

0.96

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.40

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