6-49611084-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000324.3(RHAG):c.1007T>C(p.Leu336Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
RHAG
NM_000324.3 missense
NM_000324.3 missense
Scores
6
8
5
Clinical Significance
Conservation
PhyloP100: 8.86
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.87
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RHAG | NM_000324.3 | c.1007T>C | p.Leu336Ser | missense_variant | 7/10 | ENST00000371175.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RHAG | ENST00000371175.10 | c.1007T>C | p.Leu336Ser | missense_variant | 7/10 | 1 | NM_000324.3 | P2 | |
RHAG | ENST00000646272.1 | c.1007T>C | p.Leu336Ser | missense_variant | 7/10 | A2 | |||
RHAG | ENST00000646963.1 | c.1007T>C | p.Leu336Ser | missense_variant | 7/9 | ||||
RHAG | ENST00000646939.1 | c.945+1313T>C | intron_variant |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Overhydrated hereditary stomatocytosis Uncertain:1
Uncertain significance, no assertion criteria provided | research | Department of Hematology - Research Laboratory 1, Postgraduate Institute of Medical Education and Research | Jun 27, 2017 | This variant was found in the asymptomatic mother of the index case and is likely to be not pathogenic. NM_000324.2(RHAG):c.1007 T>C was not found in 100 alleles of unrelated hematologically normal individuals. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;T;T;.
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.;.;.;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;.;.;.
REVEL
Uncertain
Sift
Uncertain
D;.;.;.;.
Sift4G
Pathogenic
D;.;D;D;.
Polyphen
P;.;.;.;D
Vest4
MutPred
Gain of disorder (P = 0.0064);Gain of disorder (P = 0.0064);Gain of disorder (P = 0.0064);Gain of disorder (P = 0.0064);Gain of disorder (P = 0.0064);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at