Genetic Variant RHAG:p.His325Arg (chr6-49611117-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_000324.3(RHAG):c.974A>G(p.His325Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,613,586 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

RHAG
NM_000324.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.60

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHAG	NM_000324.3 link	c.974A>G	p.His325Arg	missense_variant	Exon 7 of 10	ENST00000371175.10	NP_000315.2	Q02094-1Q96E98

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RHAG	ENST00000371175.10 link	c.974A>G	p.His325Arg	missense_variant	Exon 7 of 10	1	NM_000324.3	ENSP00000360217.4	Q02094-1
RHAG	ENST00000646272.1 link	c.974A>G	p.His325Arg	missense_variant	Exon 7 of 10			ENSP00000494337.1	A0A2R8YEH1
RHAG	ENST00000646963.1 link	c.974A>G	p.His325Arg	missense_variant	Exon 7 of 9			ENSP00000495337.1	Q9UHG9
RHAG	ENST00000646939.1 link	c.945+1280A>G		intron_variant	Intron 6 of 8			ENSP00000494709.1	Q02094-2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152196

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251206

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135768

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000335

AC:

AN:

1461390

Hom.:

Cov.:

AF XY:

0.0000385

AC XY:

AN XY:

727040

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:

0.0000414

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74358

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Overhydrated hereditary stomatocytosis

Uncertain:1

Sep 16, 2022

Baylor Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

T;.;T;T;.

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.79

T;T;T;T;T

M_CAP

Benign

0.0080

MetaRNN

Uncertain

0.73

D;D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;.;.;.;.

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.0

D;.;.;.;.

REVEL

Benign

0.25

Sift

Benign

0.060

T;.;.;.;.

Sift4G

Benign

0.11

T;.;T;T;.

Polyphen

0.17

B;.;.;.;B

Vest4

0.42

MutPred

0.85

Loss of ubiquitination at K321 (P = 0.1055);Loss of ubiquitination at K321 (P = 0.1055);Loss of ubiquitination at K321 (P = 0.1055);Loss of ubiquitination at K321 (P = 0.1055);Loss of ubiquitination at K321 (P = 0.1055);

MVP

0.39

MPC

0.56

ClinPred

0.67

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.43

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