rs35344839
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_024596.5(MCPH1):āc.2214C>Gā(p.Pro738=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (ā ). Synonymous variant affecting the same amino acid position (i.e. P738P) has been classified as Uncertain significance.
Frequency
Consequence
NM_024596.5 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MCPH1 | NM_024596.5 | c.2214C>G | p.Pro738= | splice_region_variant, synonymous_variant | 12/14 | ENST00000344683.10 | |
ANGPT2 | NM_001118887.2 | c.*3172G>C | 3_prime_UTR_variant | 9/9 | ENST00000629816.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MCPH1 | ENST00000344683.10 | c.2214C>G | p.Pro738= | splice_region_variant, synonymous_variant | 12/14 | 1 | NM_024596.5 | P1 | |
ANGPT2 | ENST00000629816.3 | c.*3172G>C | 3_prime_UTR_variant | 9/9 | 1 | NM_001118887.2 | P4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249550Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135392
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460814Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726790
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
MCPH1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 21, 2022 | 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