chr12-105144435-A-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_015275.3(WASHC4):āc.2159A>Gā(p.Asn720Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00024 in 1,612,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_015275.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000285 AC: 43AN: 150946Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000325 AC: 81AN: 249314Hom.: 0 AF XY: 0.000333 AC XY: 45AN XY: 135282
GnomAD4 exome AF: 0.000233 AC: 341AN: 1461510Hom.: 0 Cov.: 31 AF XY: 0.000232 AC XY: 169AN XY: 727072
GnomAD4 genome AF: 0.000305 AC: 46AN: 151036Hom.: 0 Cov.: 31 AF XY: 0.000298 AC XY: 22AN XY: 73792
ClinVar
Submissions by phenotype
not specified Uncertain:3
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Variant summary: KIAA1033 c.2159A>G (p.Asn720Ser) results in a conservative amino acid change located in the WASH complex subunit 7, central domain (IPR028282) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00031 in 279898 control chromosomes. To our knowledge, no occurrence of c.2159A>G in individuals affected with Mental Retardation, Autosomal Recessive 43 and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, citing the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. -
The c.2159A>G (p.N720S) alteration is located in exon 21 (coding exon 21) of the KIAA1033 gene. This alteration results from a A to G substitution at nucleotide position 2159, causing the asparagine (N) at amino acid position 720 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
WASHC4-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at