8-6643230-C-T

Variant names:

• chr8-6643230-C-T
• rs2433149
• NM_024596.5:c.*181C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024596.5(MCPH1):​c.*181C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MCPH1 NM_024596.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165
• Publications: 9 publications found

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]

MCPH1-AS1 (HGNC:51655): (MCPH1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCPH1	NM_024596.5	c.*181C>T		3_prime_UTR_variant	Exon 14 of 14	ENST00000344683.10	NP_078872.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCPH1	ENST00000344683.10	c.*181C>T		3_prime_UTR_variant	Exon 14 of 14	1	NM_024596.5	ENSP00000342924.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 512544 Hom.: 0 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 275116

African (AFR) AF: 0.00 AC: 0 AN: 14002

American (AMR) AF: 0.00 AC: 0 AN: 27058

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17786

East Asian (EAS) AF: 0.00 AC: 0 AN: 31588

South Asian (SAS) AF: 0.00 AC: 0 AN: 55670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33844

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2898

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 301104

Other (OTH) AF: 0.00 AC: 0 AN: 28594

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 931

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.97
PhyloP100		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2433149; hg19: chr8-6500751;