chr17-5426280-G-A
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Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_001033002.4(RPAIN):c.470G>A(p.Gly157Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,770 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 (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
RPAIN
NM_001033002.4 missense
NM_001033002.4 missense
Scores
9
8
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 6.38
Genes affected
RPAIN (HGNC:28641): (RPA interacting protein) Predicted to enable metal ion binding activity. Acts upstream of or within several processes, including DNA metabolic process; protein import into nucleus; and response to UV. Located in PML body; cytoplasm; and fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]
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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, 0.968
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RPAIN | NM_001033002.4 | c.470G>A | p.Gly157Asp | missense_variant | 5/7 | ENST00000381209.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RPAIN | ENST00000381209.8 | c.470G>A | p.Gly157Asp | missense_variant | 5/7 | 1 | NM_001033002.4 | P1 | |
ENST00000575890.1 | n.1584-787C>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251484Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135918
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GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461770Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727196
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GnomAD4 genome Cov.: 32
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;T;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;M;M
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Uncertain
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
D;.;.
Vest4
MutPred
Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);
MVP
MPC
0.59
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
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