6-116588862-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The ENST00000466444.7(RWDD1):c.291G>A(p.Met97Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,542,680 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000010 ( 0 hom. )
Consequence
RWDD1
ENST00000466444.7 missense
ENST00000466444.7 missense
Scores
2
12
5
Clinical Significance
Conservation
PhyloP100: 8.09
Genes affected
RWDD1 (HGNC:20993): (RWD domain containing 1) Predicted to be involved in several processes, including cellular response to lipid; cytoplasmic translation; and positive regulation of androgen receptor activity. Predicted to be located in cytoplasm. Predicted to be part of polysome. [provided by Alliance of Genome Resources, Apr 2022]
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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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RWDD1 | NM_015952.4 | c.291G>A | p.Met97Ile | missense_variant | 4/7 | ENST00000466444.7 | NP_057036.2 | |
RWDD1 | NM_001007464.3 | c.3G>A | p.Met1? | start_lost | 5/8 | NP_001007465.1 | ||
RWDD1 | NM_016104.4 | c.3G>A | p.Met1? | start_lost | 6/9 | NP_057188.2 | ||
RWDD1 | XM_047418863.1 | c.3G>A | p.Met1? | start_lost | 6/9 | XP_047274819.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RWDD1 | ENST00000466444.7 | c.291G>A | p.Met97Ile | missense_variant | 4/7 | 1 | NM_015952.4 | ENSP00000420357 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 151896Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000509 AC: 1AN: 196280Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 107810
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GnomAD4 exome AF: 0.0000101 AC: 14AN: 1390784Hom.: 0 Cov.: 28 AF XY: 0.0000101 AC XY: 7AN XY: 690284
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 151896Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2AN XY: 74208
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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 | May 28, 2023 | The c.291G>A (p.M97I) alteration is located in exon 4 (coding exon 4) of the RWDD1 gene. This alteration results from a G to A substitution at nucleotide position 291, causing the methionine (M) at amino acid position 97 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.;.
MutationTaster
Benign
D;N;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;N;D;N
REVEL
Uncertain
Sift
Benign
T;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D
Polyphen
B;.;.;.;.
Vest4
MutPred
Gain of helix (P = 0.132);.;.;.;.;
MVP
MPC
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