20-5992543-A-G

Position:

• chr20-5992543-A-G

Variant summary

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

The ENST00000610722.4(MCM8):​c.2241-963A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0688 in 152,210 control chromosomes in the GnomAD database, including 423 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 0.069 (423 hom., cov: 32)
• Consequence: MCM8 ENST00000610722.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.482

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]

MCM8-AS1 (HGNC:51230): (MCM8 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.095 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCM8	NM_032485.6	c.2241-963A>G		intron_variant		ENST00000610722.4	NP_115874.3
MCM8-AS1	NR_110101.1	n.458-1075T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCM8	ENST00000610722.4	c.2241-963A>G		intron_variant		1	NM_032485.6	ENSP00000478141	P1
MCM8-AS1	ENST00000613522.1	n.458-1075T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0689 AC: 10472 AN: 152092 Hom.: 422 Cov.: 32

Gnomad AFR AF: 0.0222

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0567

Gnomad ASJ AF: 0.0473

Gnomad EAS AF: 0.0925

Gnomad SAS AF: 0.0813

Gnomad FIN AF: 0.0796

Gnomad MID AF: 0.0446

Gnomad NFE AF: 0.0970

Gnomad OTH AF: 0.0589

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

GnomAD4 genome AF: 0.0688 AC: 10467 AN: 152210 Hom.: 423 Cov.: 32 AF XY: 0.0685 AC XY: 5095 AN XY: 74420

Gnomad4 AFR AF: 0.0221

Gnomad4 AMR AF: 0.0568

Gnomad4 ASJ AF: 0.0473

Gnomad4 EAS AF: 0.0921

Gnomad4 SAS AF: 0.0810

Gnomad4 FIN AF: 0.0796

Gnomad4 NFE AF: 0.0970

Gnomad4 OTH AF: 0.0583

Alfa AF: 0.0684 Hom.: 58

Bravo AF: 0.0667

Asia WGS AF: 0.0620 AC: 213 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.89

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: rs6139886; hg19: chr20-5973189;