Variant 20-5952004-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_032485.6(MCM8):c.-5-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0209 in 1,606,112 control chromosomes in the GnomAD database, including 548 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.019 ( 52 hom., cov: 32)

Exomes 𝑓: 0.021 ( 496 hom. )

Consequence

MCM8
NM_032485.6 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00006245

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.606

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 20-5952004-C-T is Benign according to our data. Variant chr20-5952004-C-T is described in ClinVar as [Benign]. Clinvar id is 1270703.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MCM8	NM_032485.6 linkuse as main transcript	c.-5-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000610722.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCM8	ENST00000610722.4 linkuse as main transcript	c.-5-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_032485.6	P1	Q9UJA3-1

Frequencies

GnomAD3 genomes

AF:

0.0190

AC:

2893

AN:

151966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00532

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0497

Gnomad ASJ

AF:

0.00750

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00457

Gnomad FIN

AF:

0.0479

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0191

Gnomad OTH

AF:

0.0202

GnomAD3 exomes

AF:

0.0264

AC:

6486

AN:

245514

Hom.:

190

AF XY:

0.0233

AC XY:

3100

AN XY:

132850

show subpopulations

Gnomad AFR exome

AF:

0.00475

Gnomad AMR exome

AF:

0.0891

Gnomad ASJ exome

AF:

0.00795

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00457

Gnomad FIN exome

AF:

0.0494

Gnomad NFE exome

AF:

0.0185

Gnomad OTH exome

AF:

0.0232

GnomAD4 exome

AF:

0.0211

AC:

30624

AN:

1454028

Hom.:

496

Cov.:

AF XY:

0.0203

AC XY:

14684

AN XY:

723410

show subpopulations

Gnomad4 AFR exome

AF:

0.00382

Gnomad4 AMR exome

AF:

0.0859

Gnomad4 ASJ exome

AF:

0.00801

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00525

Gnomad4 FIN exome

AF:

0.0509

Gnomad4 NFE exome

AF:

0.0201

Gnomad4 OTH exome

AF:

0.0198

GnomAD4 genome

AF:

0.0191

AC:

2904

AN:

152084

Hom.:

Cov.:

AF XY:

0.0200

AC XY:

1489

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.00530

Gnomad4 AMR

AF:

0.0504

Gnomad4 ASJ

AF:

0.00750

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00478

Gnomad4 FIN

AF:

0.0479

Gnomad4 NFE

AF:

0.0191

Gnomad4 OTH

AF:

0.0195

Alfa

AF:

0.0218

Hom.:

Bravo

AF:

0.0204

Asia WGS

AF:

0.00982

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 14, 2020

This variant is associated with the following publications: (PMID: 32155011) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

Cadd

Benign

2.7

Dann

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000062

dbscSNV1_RF

Benign

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over