1-25389003-G-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_020485.8(RHCE):āc.912C>Gā(p.Ile304Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 30)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
RHCE
NM_020485.8 missense
NM_020485.8 missense
Scores
11
6
Clinical Significance
Conservation
PhyloP100: 0.953
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 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RHCE | NM_020485.8 | c.912C>G | p.Ile304Met | missense_variant | 6/10 | ENST00000294413.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RHCE | ENST00000294413.13 | c.912C>G | p.Ile304Met | missense_variant | 6/10 | 1 | NM_020485.8 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 30
GnomAD3 genomes
?
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30
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251390Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135888
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461880Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727242
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GnomAD4 genome ? Cov.: 30
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ExAC
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 27, 2024 | The c.912C>G (p.I304M) alteration is located in exon 6 (coding exon 6) of the RHCE gene. This alteration results from a C to G substitution at nucleotide position 912, causing the isoleucine (I) at amino acid position 304 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;N;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N;D;N;D
REVEL
Uncertain
Sift
Benign
T;D;D;D;D
Sift4G
Uncertain
D;T;D;D;D
Polyphen
1.0, 0.99
.;D;.;D;.
Vest4
MutPred
Loss of glycosylation at S305 (P = 0.0693);.;.;Loss of glycosylation at S305 (P = 0.0693);Loss of glycosylation at S305 (P = 0.0693);
MVP
MPC
ClinPred
D
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at