rs762679
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_182746.3(MCM4):c.1948T>A(p.Leu650Met) variant causes a missense change. The variant allele was found at a frequency of 0.862 in 1,613,868 control chromosomes in the GnomAD database, including 600,719 homozygotes. 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 Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L650T) has been classified as Uncertain significance.
Frequency
Consequence
NM_182746.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MCM4 | NM_182746.3 | c.1948T>A | p.Leu650Met | missense_variant | 14/17 | ENST00000649973.1 | |
MCM4 | NM_005914.4 | c.1948T>A | p.Leu650Met | missense_variant | 13/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MCM4 | ENST00000649973.1 | c.1948T>A | p.Leu650Met | missense_variant | 14/17 | NM_182746.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.883 AC: 134338AN: 152140Hom.: 59422 Cov.: 33
GnomAD3 exomes AF: 0.872 AC: 219014AN: 251290Hom.: 95914 AF XY: 0.867 AC XY: 117747AN XY: 135806
GnomAD4 exome AF: 0.860 AC: 1256733AN: 1461610Hom.: 541232 Cov.: 45 AF XY: 0.860 AC XY: 625052AN XY: 727120
GnomAD4 genome ? AF: 0.883 AC: 134465AN: 152258Hom.: 59487 Cov.: 33 AF XY: 0.883 AC XY: 65737AN XY: 74434
ClinVar
Submissions by phenotype
Primary immunodeficiency with natural-killer cell deficiency and adrenal insufficiency Benign:3
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan | Nov 12, 2023 | This variant is classified as Benign based on local population frequency. This variant was detected in 99% of patients studied by a panel of primary immunodeficiencies. Number of patients: 95. Only high quality variants are reported. - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at