1-25301594-G-A
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_016124.6(RHD):c.709G>A(p.Ala237Thr) variant causes a missense change. 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 Affects (no stars).
Frequency
Genomes: not found (cov: 21)
Consequence
RHD
NM_016124.6 missense
NM_016124.6 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 4.39
Genes affected
RHD (HGNC:10009): (Rh blood group D antigen) The Rh blood group system is the second most clinically significant of the blood groups, second only to ABO. It is also the most polymorphic of the blood groups, with variations due to deletions, gene conversions, and missense mutations. The Rh blood group includes this gene, which encodes the RhD protein, and a second gene that encodes both the RhC and RhE antigens on a single polypeptide. The two genes, and a third unrelated gene, are found in a cluster on chromosome 1. The classification of Rh-positive and Rh-negative individuals is determined by the presence or absence of the highly immunogenic RhD protein on the surface of erythrocytes. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
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, 0.914
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| RHD | NM_016124.6 | c.709G>A | p.Ala237Thr | missense_variant | Exon 5 of 10 | ENST00000328664.9 | NP_057208.3 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
21
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome
GnomAD4 genome
Cov.:
21
ClinVar
Significance: Affects
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
weakened D expression by serology Other:1
Jul 01, 2021
Australian Red Cross Blood Service
Significance: Affects
Review Status: no assertion criteria provided
Collection Method: research
We have found this nucleotide change RHDc.709G>A in three different samples. All showing weakened D expression on serology. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.;.;.;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;.
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;M;M;M;.;M;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;.;D;D;D;D;D;D
REVEL
Benign
Sift
Uncertain
D;.;.;T;T;T;T;T;T
Sift4G
Benign
T;.;T;T;T;T;T;T;T
Polyphen
D;.;D;.;.;.;.;.;D
Vest4
MutPred
Gain of ubiquitination at K235 (P = 0.0972);Gain of ubiquitination at K235 (P = 0.0972);Gain of ubiquitination at K235 (P = 0.0972);Gain of ubiquitination at K235 (P = 0.0972);Gain of ubiquitination at K235 (P = 0.0972);Gain of ubiquitination at K235 (P = 0.0972);Gain of ubiquitination at K235 (P = 0.0972);Gain of ubiquitination at K235 (P = 0.0972);Gain of ubiquitination at K235 (P = 0.0972);
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
Publications
No publications associated with this variant yet.