rs121434305
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_024596.5(MCPH1):āc.74C>Gā(p.Ser25Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000753 in 1,461,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (ā ). Synonymous variant affecting the same amino acid position (i.e. S25S) has been classified as Likely benign.
Frequency
Consequence
NM_024596.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MCPH1 | NM_024596.5 | c.74C>G | p.Ser25Ter | stop_gained | 2/14 | ENST00000344683.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MCPH1 | ENST00000344683.10 | c.74C>G | p.Ser25Ter | stop_gained | 2/14 | 1 | NM_024596.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249568Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135406
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461784Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727202
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Microcephaly 1, primary, autosomal recessive Pathogenic:1Other:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 01, 2006 | - - |
not provided, no classification provided | literature only | GeneReviews | - | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 18, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 3454). This premature translational stop signal has been observed in individual(s) with clinical features of MCPH1-related conditions (PMID: 12046007). This variant is present in population databases (rs121434305, gnomAD 0.004%). This sequence change creates a premature translational stop signal (p.Ser25*) in the MCPH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MCPH1 are known to be pathogenic (PMID: 20978018). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at