Variant chr6-118815367-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_017696.3(MCM9):c.2889C>T(p.Asp963=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,550,412 control chromosomes in the GnomAD database, including 151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0089 ( 7 hom., cov: 31)

Exomes 𝑓: 0.012 ( 144 hom. )

Consequence

MCM9
NM_017696.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.102

Variant links:

Genes affected

MCM9 (HGNC:21484): (minichromosome maintenance 9 homologous recombination repair factor) The protein encoded by this gene is a member of the mini-chromosome maintenance (MCM) protein family that are essential for the initiation of eukaryotic genome replication. Binding of this protein to chromatin has been shown to be a pre-requisite for recruiting the MCM2-7 helicase to DNA replication origins. This protein also binds, and is a positive regulator of, the chromatin licensing and DNA replication factor 1, CDT1. [provided by RefSeq, Nov 2010]

MCM9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 6-118815367-G-A is Benign according to our data. Variant chr6-118815367-G-A is described in ClinVar as [Benign]. Clinvar id is 3067201.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.102 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MCM9	NM_017696.3 linkuse as main transcript	c.2889C>T	p.Asp963=	synonymous_variant	14/14	ENST00000619706.5	NP_060166.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MCM9	ENST00000619706.5 linkuse as main transcript	c.2889C>T	p.Asp963=	synonymous_variant	14/14	5	NM_017696.3	ENSP00000480469	P1	Q9NXL9-1
MCM9	ENST00000316316.10 linkuse as main transcript	c.2889C>T	p.Asp963=	synonymous_variant	13/13	5		ENSP00000314505	P1	Q9NXL9-1

Frequencies

GnomAD3 genomes

AF:

0.00888

AC:

1350

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00224

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.00655

Gnomad ASJ

AF:

0.00894

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0116

Gnomad FIN

AF:

0.0108

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0138

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.0102

AC:

1518

AN:

148804

Hom.:

AF XY:

0.0107

AC XY:

860

AN XY:

80028

show subpopulations

Gnomad AFR exome

AF:

0.00250

Gnomad AMR exome

AF:

0.00518

Gnomad ASJ exome

AF:

0.00802

Gnomad EAS exome

AF:

0.000185

Gnomad SAS exome

AF:

0.0109

Gnomad FIN exome

AF:

0.0144

Gnomad NFE exome

AF:

0.0142

Gnomad OTH exome

AF:

0.00886

GnomAD4 exome

AF:

0.0120

AC:

16724

AN:

1398254

Hom.:

144

Cov.:

AF XY:

0.0120

AC XY:

8258

AN XY:

689640

show subpopulations

Gnomad4 AFR exome

AF:

0.00190

Gnomad4 AMR exome

AF:

0.00524

Gnomad4 ASJ exome

AF:

0.00799

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.0103

Gnomad4 FIN exome

AF:

0.0155

Gnomad4 NFE exome

AF:

0.0131

Gnomad4 OTH exome

AF:

0.00886

GnomAD4 genome

AF:

0.00887

AC:

1349

AN:

152158

Hom.:

Cov.:

AF XY:

0.00854

AC XY:

635

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00221

Gnomad4 AMR

AF:

0.00648

Gnomad4 ASJ

AF:

0.00894

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0118

Gnomad4 FIN

AF:

0.0108

Gnomad4 NFE

AF:

0.0138

Gnomad4 OTH

AF:

0.00664

Alfa

AF:

0.0120

Hom.:

Bravo

AF:

0.00830

Asia WGS

AF:

0.00375

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

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

MCM9: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.0

DANN

Benign

0.25

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

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