Genetic Variant RHAG:p.Gly389Arg (chr6-49606895-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000324.3(RHAG):c.1165G>A(p.Gly389Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,611,910 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., 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: 3.82

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RHAG	NM_000324.3 link	c.1165G>A	p.Gly389Arg	missense_variant	Exon 9 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.1165G>A	p.Gly389Arg	missense_variant	Exon 9 of 10	1	NM_000324.3	ENSP00000360217.4	Q02094-1
RHAG	ENST00000646272.1 link	c.1165G>A	p.Gly389Arg	missense_variant	Exon 9 of 10			ENSP00000494337.1	A0A2R8YEH1
RHAG	ENST00000646939.1 link	c.1043G>A	p.Gly348Glu	missense_variant	Exon 8 of 9			ENSP00000494709.1	Q02094-2
RHAG	ENST00000646963.1 link	c.1138+255G>A		intron_variant	Intron 8 of 8			ENSP00000495337.1	Q9UHG9

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152034

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1459876

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726396

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

33428

Gnomad4 AMR exome

AF:

0.00

AC:

AN:

44686

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26116

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39684

Gnomad4 SAS exome

AF:

0.00

AC:

AN:

86206

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

53390

Gnomad4 NFE exome

AF:

0.00000360

AC:

AN:

1110310

Gnomad4 Remaining exome

AF:

0.00

AC:

AN:

60296

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152034

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.00

AC:

AN:

Gnomad4 AMR

AF:

0.00

AC:

AN:

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.0000147

AC:

0.0000147033

AN:

0.0000147033

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000325

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Jan 24, 2023

Revvity Omics, Revvity

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

0.12

BayesDel_addAF

Benign

-0.074

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

0.080

Eigen_PC

Benign

0.012

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.21

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.44

MetaSVM

Benign

-1.1

ClinPred

0.99

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

Mutation Taster

=83/17

polymorphism

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