8-6621488-C-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_024596.5(MCPH1):āc.2249C>Gā(p.Pro750Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,614,004 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 (ā ).
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MCPH1 | NM_024596.5 | c.2249C>G | p.Pro750Arg | missense_variant | 13/14 | ENST00000344683.10 | NP_078872.3 | |
MCPH1-AS1 | NR_125386.1 | n.377G>C | non_coding_transcript_exon_variant | 3/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MCPH1 | ENST00000344683.10 | c.2249C>G | p.Pro750Arg | missense_variant | 13/14 | 1 | NM_024596.5 | ENSP00000342924 | P1 | |
MCPH1-AS1 | ENST00000661193.1 | n.1055-1264G>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152202Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 249220Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135248
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461802Hom.: 0 Cov.: 48 AF XY: 0.0000138 AC XY: 10AN XY: 727212
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152202Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74344
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 27, 2022 | The c.2249C>G (p.P750R) alteration is located in exon 13 (coding exon 13) of the MCPH1 gene. This alteration results from a C to G substitution at nucleotide position 2249, causing the proline (P) at amino acid position 750 to be replaced by an arginine (R). 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