rs119490107
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5
The ENST00000336148.10(RAD54B):c.1252G>T(p.Asp418Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,612,854 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 Pathogenic (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000041 ( 0 hom. )
Consequence
RAD54B
ENST00000336148.10 missense
ENST00000336148.10 missense
Scores
9
6
4
Clinical Significance
Conservation
PhyloP100: 7.71
Genes affected
RAD54B (HGNC:17228): (RAD54 homolog B) The protein encoded by this gene belongs to the DEAD-like helicase superfamily. It shares similarity with Saccharomyces cerevisiae RAD54 and RDH54, both of which are involved in homologous recombination and repair of DNA. This protein binds to double-stranded DNA, and displays ATPase activity in the presence of DNA. This gene is highly expressed in testis and spleen, which suggests active roles in meiotic and mitotic recombination. Homozygous mutations of this gene were observed in primary lymphoma and colon cancer. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.76
PP5
Variant 8-94399540-C-A is Pathogenic according to our data. Variant chr8-94399540-C-A is described in ClinVar as [Pathogenic]. Clinvar id is 5639.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RAD54B | NM_012415.3 | c.1252G>T | p.Asp418Tyr | missense_variant | 8/15 | ENST00000336148.10 | NP_036547.1 | |
RAD54B | NM_001205263.2 | c.700G>T | p.Asp234Tyr | missense_variant | 6/13 | NP_001192192.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RAD54B | ENST00000336148.10 | c.1252G>T | p.Asp418Tyr | missense_variant | 8/15 | 1 | NM_012415.3 | ENSP00000336606 | P1 | |
RAD54B | ENST00000463267.5 | c.*876G>T | 3_prime_UTR_variant, NMD_transcript_variant | 9/11 | 1 | ENSP00000430808 | ||||
RAD54B | ENST00000523192.1 | n.44G>T | non_coding_transcript_exon_variant | 1/2 | 2 | |||||
FSBP | ENST00000517506.2 | c.*932G>T | 3_prime_UTR_variant, NMD_transcript_variant | 6/12 | 5 | ENSP00000462684 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151996Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000280 AC: 7AN: 249930Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135112
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GnomAD4 exome AF: 0.0000411 AC: 60AN: 1460858Hom.: 0 Cov.: 31 AF XY: 0.0000427 AC XY: 31AN XY: 726746
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 151996Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74232
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Carcinoma of colon Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 03, 1999 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
A
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;.
REVEL
Pathogenic
Sift
Uncertain
D;.
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MutPred
Gain of ubiquitination at K421 (P = 0.1688);.;
MVP
MPC
ClinPred
D
GERP RS
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