chr8-6406660-C-T
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_024596.5(MCPH1):c.-8C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,611,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
MCPH1
NM_024596.5 5_prime_UTR
NM_024596.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.71
Genes affected
MCPH1 (HGNC:6954): (microcephalin 1) This gene encodes a DNA damage response protein. The encoded protein may play a role in G2/M checkpoint arrest via maintenance of inhibitory phosphorylation of cyclin-dependent kinase 1. Mutations in this gene have been associated with primary autosomal recessive microcephaly 1 and premature chromosome condensation syndrome. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
BP6
Variant 8-6406660-C-T is Benign according to our data. Variant chr8-6406660-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3050955.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MCPH1 | NM_024596.5 | c.-8C>T | 5_prime_UTR_variant | 1/14 | ENST00000344683.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MCPH1 | ENST00000344683.10 | c.-8C>T | 5_prime_UTR_variant | 1/14 | 1 | NM_024596.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152182Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000125 AC: 3AN: 240558Hom.: 0 AF XY: 0.0000152 AC XY: 2AN XY: 131986
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GnomAD4 exome AF: 0.00000617 AC: 9AN: 1459808Hom.: 0 Cov.: 33 AF XY: 0.00000689 AC XY: 5AN XY: 726184
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74336
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
MCPH1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 14, 2020 | 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
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BayesDel_noAF
Benign
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Benign
DANN
Benign
RBP_binding_hub_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at