rs202004426
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_024596.5(MCPH1):c.1351G>A(p.Glu451Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000598 in 1,614,238 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_024596.5 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 |
---|---|---|---|---|---|---|---|
MCPH1 | NM_024596.5 | c.1351G>A | p.Glu451Lys | missense_variant | 8/14 | ENST00000344683.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MCPH1 | ENST00000344683.10 | c.1351G>A | p.Glu451Lys | missense_variant | 8/14 | 1 | NM_024596.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000381 AC: 58AN: 152230Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00123 AC: 306AN: 249498Hom.: 3 AF XY: 0.00164 AC XY: 222AN XY: 135380
GnomAD4 exome AF: 0.000620 AC: 907AN: 1461890Hom.: 9 Cov.: 51 AF XY: 0.000908 AC XY: 660AN XY: 727248
GnomAD4 genome ? AF: 0.000381 AC: 58AN: 152348Hom.: 0 Cov.: 33 AF XY: 0.000523 AC XY: 39AN XY: 74510
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 04, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 18, 2017 | - - |
Microcephaly 1, primary, autosomal recessive Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
MCPH1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 17, 2020 | 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at