1-156378315-T-C
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_020407.5(RHBG):āc.589T>Cā(p.Ser197Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,614,094 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 Uncertain significance (ā ).
Frequency
Genomes: š 0.000026 ( 0 hom., cov: 31)
Exomes š: 0.0000027 ( 0 hom. )
Consequence
RHBG
NM_020407.5 missense
NM_020407.5 missense
Scores
1
7
4
Clinical Significance
Conservation
PhyloP100: 2.10
Genes affected
RHBG (HGNC:14572): (Rh family B glycoprotein) This gene encodes one of two non-erythroid members of the Rhesus (Rh) protein family. Non-erythroid Rh protein family members are mainly expressed in the kidney and belong to the methylammonium-ammonium permease/ammonia transporters superfamily. All Rh family proteins are predicted to be transmembrane proteins with 12 membrane spanning domains and intracytoplasmic N- and C-termini. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.943
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RHBG | NM_020407.5 | c.589T>C | p.Ser197Pro | missense_variant | 4/10 | ENST00000537040.6 | NP_065140.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RHBG | ENST00000537040.6 | c.589T>C | p.Ser197Pro | missense_variant | 4/10 | 1 | NM_020407.5 | ENSP00000441197.2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152146Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249376Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135304
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461830Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2AN XY: 727224
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152264Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74436
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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 | Apr 04, 2023 | The c.589T>C (p.S197P) alteration is located in exon 4 (coding exon 4) of the RHBG gene. This alteration results from a T to C substitution at nucleotide position 589, causing the serine (S) at amino acid position 197 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
PrimateAI
Benign
T
Sift4G
Uncertain
D
Vest4
MutPred
Loss of catalytic residue at S197 (P = 0.0605);
MVP
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