6-49619284-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PS1_ModeratePM2PP3_ModeratePP5

The NM_000324.3(RHAG):​c.236G>A​(p.Ser79Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,846 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

RHAG
NM_000324.3 missense

Scores

5
6
8

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 4.96
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PS1
Transcript NM_000324.3 (RHAG) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.938
PP5
Variant 6-49619284-C-T is Pathogenic according to our data. Variant chr6-49619284-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 13059.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RHAGNM_000324.3 linkuse as main transcriptc.236G>A p.Ser79Asn missense_variant 2/10 ENST00000371175.10 NP_000315.2 Q02094-1Q96E98
RHAGXM_011514788.2 linkuse as main transcriptc.236G>A p.Ser79Asn missense_variant 2/5 XP_011513090.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RHAGENST00000371175.10 linkuse as main transcriptc.236G>A p.Ser79Asn missense_variant 2/101 NM_000324.3 ENSP00000360217.4 Q02094-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251442
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135904
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:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461846
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727234
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:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Rh mod blood group phenotype Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMFeb 01, 1996- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.83
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.44
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
T;.;.;T;T;.
Eigen
Pathogenic
0.78
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.63
T;T;T;T;T;T
M_CAP
Benign
0.060
D
MetaRNN
Pathogenic
0.94
D;D;D;D;D;D
MetaSVM
Benign
-0.58
T
MutationAssessor
Pathogenic
3.4
M;.;M;.;.;.
MutationTaster
Benign
1.0
A;A
PrimateAI
Benign
0.45
T
PROVEAN
Uncertain
-2.4
N;.;.;.;D;.
REVEL
Uncertain
0.39
Sift
Uncertain
0.0030
D;.;.;.;D;.
Sift4G
Uncertain
0.0040
D;.;.;D;D;.
Polyphen
0.98
D;.;.;.;.;D
Vest4
0.87
MutPred
0.93
Loss of methylation at K74 (P = 0.1098);Loss of methylation at K74 (P = 0.1098);Loss of methylation at K74 (P = 0.1098);Loss of methylation at K74 (P = 0.1098);Loss of methylation at K74 (P = 0.1098);Loss of methylation at K74 (P = 0.1098);
MVP
0.55
MPC
0.85
ClinPred
0.95
D
GERP RS
5.6
Varity_R
0.50
gMVP
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.19
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.

Other links and lift over

dbSNP: rs121918586; hg19: chr6-49586997; API