19-45351328-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The ENST00000391946.7(KLC3):c.1486G>A(p.Ala496Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000738 in 1,611,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
ENST00000391946.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
KLC3 | NM_177417.3 | c.1486G>A | p.Ala496Thr | missense_variant | 13/13 | ENST00000391946.7 | NP_803136.2 | |
ERCC2 | NM_000400.4 | c.*301C>T | 3_prime_UTR_variant | 23/23 | ENST00000391945.10 | NP_000391.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
KLC3 | ENST00000391946.7 | c.1486G>A | p.Ala496Thr | missense_variant | 13/13 | 1 | NM_177417.3 | ENSP00000375810 | P4 | |
ERCC2 | ENST00000391945.10 | c.*301C>T | 3_prime_UTR_variant | 23/23 | 1 | NM_000400.4 | ENSP00000375809 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152076Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000848 AC: 21AN: 247778Hom.: 0 AF XY: 0.0000668 AC XY: 9AN XY: 134692
GnomAD4 exome AF: 0.0000760 AC: 111AN: 1459830Hom.: 0 Cov.: 36 AF XY: 0.0000716 AC XY: 52AN XY: 726412
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152076Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74282
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden | Nov 03, 2021 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 13, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at