20-5954803-C-T

Position:

• chr20-5954803-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032485.6(MCM8):​c.336+113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 649,682 control chromosomes in the GnomAD database, including 12,452 homozygotes. 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: 𝑓 0.23 (5679 hom., cov: 33)
  • Exomes 𝑓: 0.15 (6773 hom.)
• Consequence: MCM8 NM_032485.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950

Genes affected

MCM8 (HGNC:16147): (minichromosome maintenance 8 homologous recombination repair factor) The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication. The hexameric protein complex formed by the mini-chromosome maintenance proteins is a key component of the pre-replication complex and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. This protein contains the central domain that is conserved among the mini-chromosome maintenance proteins. The encoded protein may interact with other mini-chromosome maintenance proteins and play a role in DNA replication. This gene may be associated with length of reproductive lifespan and menopause. Alternatively spliced transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Jul 2013]

ENSG00000286235 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCM8	NM_032485.6	c.336+113C>T		intron_variant		ENST00000610722.4	NP_115874.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCM8	ENST00000610722.4	c.336+113C>T		intron_variant		1	NM_032485.6	ENSP00000478141.1
ENSG00000286235	ENST00000652720.1	c.336+113C>T		intron_variant				ENSP00000498784.1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34571 AN: 152040 Hom.: 5665 Cov.: 33

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.150 AC: 74571 AN: 497524 Hom.: 6773 AF XY: 0.152 AC XY: 40106 AN XY: 263034

Gnomad4 AFR exome AF: 0.455

Gnomad4 AMR exome AF: 0.166

Gnomad4 ASJ exome AF: 0.126

Gnomad4 EAS exome AF: 0.157

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.166

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.168

GnomAD4 genome AF: 0.228 AC: 34625 AN: 152158 Hom.: 5679 Cov.: 33 AF XY: 0.227 AC XY: 16919 AN XY: 74394

Gnomad4 AFR AF: 0.463

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.208

Alfa AF: 0.178 Hom.: 461

Bravo AF: 0.236

Asia WGS AF: 0.227 AC: 792 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.1
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs236115; hg19: chr20-5935449;