chr20-5978314-T-C

Position:

• chr20-5978314-T-C

Variant summary

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

The NM_032485.6(MCM8):​c.1537+297T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 138,402 control chromosomes in the GnomAD database, including 15,291 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 0.41 (15291 hom., cov: 32)
• Consequence: MCM8 NM_032485.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCM8	NM_032485.6	c.1537+297T>C		intron_variant		ENST00000610722.4	NP_115874.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCM8	ENST00000610722.4	c.1537+297T>C		intron_variant		1	NM_032485.6	ENSP00000478141	P1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 56937 AN: 138286 Hom.: 15252 Cov.: 32

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.393

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.412 AC: 57036 AN: 138402 Hom.: 15291 Cov.: 32 AF XY: 0.413 AC XY: 27715 AN XY: 67140

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.390

Alfa AF: 0.302 Hom.: 1575

Bravo AF: 0.399

Asia WGS AF: 0.401 AC: 1393 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.60

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: rs236104; hg19: chr20-5958960;