chr6-49606921-C-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5
The NM_000324.3(RHAG):c.1139G>T(p.Gly380Val) variant causes a missense, splice region 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. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Consequence
RHAG
NM_000324.3 missense, splice_region
NM_000324.3 missense, splice_region
Scores
9
5
5
Splicing: ADA: 0.9996
2
Clinical Significance
Conservation
PhyloP100: 7.50
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
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
?
Variant 6-49606921-C-A is Pathogenic according to our data. Variant chr6-49606921-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 13066.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RHAG | NM_000324.3 | c.1139G>T | p.Gly380Val | missense_variant, splice_region_variant | 9/10 | ENST00000371175.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RHAG | ENST00000371175.10 | c.1139G>T | p.Gly380Val | missense_variant, splice_region_variant | 9/10 | 1 | NM_000324.3 | P2 | |
RHAG | ENST00000646272.1 | c.1139G>T | p.Gly380Val | missense_variant, splice_region_variant | 9/10 | A2 | |||
RHAG | ENST00000646939.1 | c.1017G>T | p.Arg339Ser | missense_variant, splice_region_variant | 8/9 | ||||
RHAG | ENST00000646963.1 | c.1138+229G>T | intron_variant |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 28
GnomAD4 exome
Cov.:
28
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Rh-null, regulator type Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 1999 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
H;.;.
MutationTaster
Benign
A;A
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;.
REVEL
Uncertain
Sift
Uncertain
D;.;.
Sift4G
Pathogenic
D;.;D
Polyphen
D;.;.
Vest4
MutPred
Gain of methylation at K384 (P = 0.0989);Gain of methylation at K384 (P = 0.0989);Gain of methylation at K384 (P = 0.0989);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: 0
Find out detailed SpliceAI scores and Pangolin per-transcript scores at