rs861539
Positions:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_005432.4(XRCC3):c.722C>T(p.Thr241Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,611,814 control chromosomes in the GnomAD database, including 98,522 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.30 ( 7378 hom., cov: 32)
Exomes 𝑓: 0.35 ( 91144 hom. )
Consequence
XRCC3
NM_005432.4 missense
NM_005432.4 missense
Scores
1
17
Clinical Significance
Conservation
PhyloP100: 0.797
Genes affected
XRCC3 (HGNC:12830): (X-ray repair cross complementing 3) This gene encodes a member of the RecA/Rad51-related protein family that participates in homologous recombination to maintain chromosome stability and repair DNA damage. This gene functionally complements Chinese hamster irs1SF, a repair-deficient mutant that exhibits hypersensitivity to a number of different DNA-damaging agents and is chromosomally unstable. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]
KLC1 (HGNC:6387): (kinesin light chain 1) Conventional kinesin is a tetrameric molecule composed of two heavy chains and two light chains, and transports various cargos along microtubules toward their plus ends. The heavy chains provide the motor activity, while the light chains bind to various cargos. This gene encodes a member of the kinesin light chain family. It associates with kinesin heavy chain through an N-terminal domain, and six tetratricopeptide repeat (TPR) motifs are thought to be involved in binding of cargos such as vesicles, mitochondria, and the Golgi complex. Thus, kinesin light chains function as adapter molecules and not motors per se. Although previously named "kinesin 2", this gene is not a member of the kinesin-2 / kinesin heavy chain subfamily of kinesin motor proteins. Extensive alternative splicing produces isoforms with different C-termini that are proposed to bind to different cargos; however, the full-length nature and/or biological validity of most of these variants have not been determined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.016989827).
BP6
Variant 14-103699416-G-A is Benign according to our data. Variant chr14-103699416-G-A is described in ClinVar as [Benign]. Clinvar id is 8944.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
XRCC3 | NM_005432.4 | c.722C>T | p.Thr241Met | missense_variant | 8/10 | ENST00000555055.6 | |
KLC1 | NM_001394837.1 | c.1849-1239G>A | intron_variant | ENST00000334553.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
XRCC3 | ENST00000555055.6 | c.722C>T | p.Thr241Met | missense_variant | 8/10 | 1 | NM_005432.4 | P1 | |
KLC1 | ENST00000334553.11 | c.1849-1239G>A | intron_variant | 5 | NM_001394837.1 |
Frequencies
GnomAD3 genomes AF: 0.298 AC: 45211AN: 151816Hom.: 7375 Cov.: 32
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GnomAD3 exomes AF: 0.290 AC: 71621AN: 246952Hom.: 11812 AF XY: 0.298 AC XY: 40018AN XY: 134296
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GnomAD4 exome AF: 0.346 AC: 504514AN: 1459878Hom.: 91144 Cov.: 56 AF XY: 0.345 AC XY: 250452AN XY: 726268
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GnomAD4 genome AF: 0.298 AC: 45218AN: 151936Hom.: 7378 Cov.: 32 AF XY: 0.291 AC XY: 21629AN XY: 74296
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1419
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1498
ESP6500AA
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ClinVar
Significance: Benign
Submissions summary: Benign:2Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
XRCC3-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 17, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 08, 2023 | - - |
Melanoma, cutaneous malignant, susceptibility to, 6 Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Oct 15, 2000 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
.;.;.;T;T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;L;.
MutationTaster
Benign
P;P;P;P;P;P;P;P;P;P;P;P
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T
Sift4G
Benign
T;T;T;T;T
Polyphen
P;P;P;P;.
Vest4
MPC
0.19
ClinPred
T
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