chr8-6499910-A-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_024596.5(MCPH1):c.2195A>C(p.His732Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000613 in 1,613,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. H732H) has been classified as Likely benign.
Frequency
Consequence
NM_024596.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MCPH1 | NM_024596.5 | c.2195A>C | p.His732Pro | missense_variant | 12/14 | ENST00000344683.10 | |
ANGPT2 | NM_001118887.2 | c.*3191T>G | 3_prime_UTR_variant | 9/9 | ENST00000629816.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MCPH1 | ENST00000344683.10 | c.2195A>C | p.His732Pro | missense_variant | 12/14 | 1 | NM_024596.5 | P1 | |
ANGPT2 | ENST00000629816.3 | c.*3191T>G | 3_prime_UTR_variant | 9/9 | 1 | NM_001118887.2 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000315 AC: 48AN: 152166Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000761 AC: 19AN: 249580Hom.: 0 AF XY: 0.0000739 AC XY: 10AN XY: 135406
GnomAD4 exome AF: 0.0000349 AC: 51AN: 1461410Hom.: 0 Cov.: 30 AF XY: 0.0000330 AC XY: 24AN XY: 727010
GnomAD4 genome ? AF: 0.000315 AC: 48AN: 152286Hom.: 0 Cov.: 33 AF XY: 0.000269 AC XY: 20AN XY: 74466
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 06, 2023 | The c.2195A>C (p.H732P) alteration is located in exon 12 (coding exon 12) of the MCPH1 gene. This alteration results from a A to C substitution at nucleotide position 2195, causing the histidine (H) at amino acid position 732 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at