rs6139886

Variant names:

• chr20-5992543-A-G
• rs6139886
• NM_032485.6:c.2241-963A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032485.6(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 NM_032485.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.482
• Publications: 1 publications found

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:):

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MCM8	NM_032485.6	c.2241-963A>G		intron_variant	Intron 17 of 18	ENST00000610722.4	NP_115874.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCM8	ENST00000610722.4	c.2241-963A>G		intron_variant	Intron 17 of 18	1	NM_032485.6	ENSP00000478141.1
ENSG00000286235	ENST00000652720.1	c.2241-963A>G		intron_variant	Intron 17 of 23			ENSP00000498784.1

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

African (AFR) AF: 0.0221 AC: 919 AN: 41562

American (AMR) AF: 0.0568 AC: 868 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0473 AC: 164 AN: 3466

East Asian (EAS) AF: 0.0921 AC: 478 AN: 5190

South Asian (SAS) AF: 0.0810 AC: 391 AN: 4828

European-Finnish (FIN) AF: 0.0796 AC: 844 AN: 10602

Middle Eastern (MID) AF: 0.0411 AC: 12 AN: 292

European-Non Finnish (NFE) AF: 0.0970 AC: 6593 AN: 67970

Other (OTH) AF: 0.0583 AC: 123 AN: 2110

Alfa AF: 0.0670 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
PhyloP100		0.48
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6139886; hg19: chr20-5973189;