1-25389032-T-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_020485.8(RHCE):āc.883A>Gā(p.Met295Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,886 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 Affects (no stars).
Frequency
Genomes: not found (cov: 30)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
RHCE
NM_020485.8 missense
NM_020485.8 missense
Scores
3
8
6
Clinical Significance
Conservation
PhyloP100: 4.94
Genes affected
RHCE (HGNC:10008): (Rh blood group CcEe antigens) 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 both the RhC and RhE antigens on a single polypeptide and a second gene which encodes the RhD protein. 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. A mutation in this gene results in amorph-type Rh-null disease. Alternative splicing of this gene results in multiple transcript variants encoding several different isoforms. [provided by RefSeq, Aug 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.834
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RHCE | NM_020485.8 | c.883A>G | p.Met295Val | missense_variant | 6/10 | ENST00000294413.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RHCE | ENST00000294413.13 | c.883A>G | p.Met295Val | missense_variant | 6/10 | 1 | NM_020485.8 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 30
GnomAD3 genomes
?
Cov.:
30
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461886Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727244
GnomAD4 exome
AF:
AC:
2
AN:
1461886
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
727244
Gnomad4 AFR exome
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Gnomad4 AMR exome
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Gnomad4 ASJ exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 NFE exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 30
GnomAD4 genome
?
Cov.:
30
ClinVar
Significance: Affects
Submissions summary: Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
altered RhC expression Other:1
Affects, no assertion criteria provided | research | Australian Red Cross Blood Service | - | Reduced RhC antigen expression observed in patient. genbank submission JX420300.1 (Author: Bugert,P., Rink,G., Goebel,M. and Scharberg,E.A.) reports c.883A>G as an RhC variant. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T;T
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D;T;D
Sift4G
Uncertain
D;D;D;D;D
Polyphen
1.0, 1.0
.;D;.;D;.
Vest4
MutPred
Gain of helix (P = 0.0496);.;.;Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);
MVP
MPC
ClinPred
D
GERP RS
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.