Genetic Variant ENST00000518221.5:c.-14-313_-14-312insC (chr8-47960818-T-TC) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000518221.5(MCM4):c.-14-313_-14-312insC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 331,500 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000089 ( 0 hom. )

Consequence

MCM4
ENST00000518221.5 intron

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.71

Publications

0 publications found

Variant links:

Genes affected

MCM4 (HGNC:6947): (minichromosome maintenance complex component 4) 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 MCM proteins is a key component of the pre-replication complex (pre_RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. The MCM complex consisting of this protein and MCM2, 6 and 7 proteins possesses DNA helicase activity, and may act as a DNA unwinding enzyme. The phosphorylation of this protein by CDC2 kinase reduces the DNA helicase activity and chromatin binding of the MCM complex. This gene is mapped to a region on the chromosome 8 head-to-head next to the PRKDC/DNA-PK, a DNA-activated protein kinase involved in the repair of DNA double-strand breaks. Alternatively spliced transcript variants encoding the same protein have been reported. [provided by RefSeq, Jul 2008]

MCM4 Gene-Disease associations (from GenCC):

primary immunodeficiency with natural-killer cell deficiency and adrenal insufficiency
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen

MCM4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000518221.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCM4	NM_182746.3	MANE Select	c.-211_-210insC		upstream_gene	N/A	NP_877423.1	P33991
	MCM4	NM_005914.4		c.-327_-326insC		upstream_gene	N/A	NP_005905.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MCM4	ENST00000518221.5	TSL:4	c.-14-313_-14-312insC	intron	N/A	ENSP00000430329.1	E5RFR3
MCM4	ENST00000649973.1	MANE Select	c.-211_-210insC	upstream_gene	N/A	ENSP00000496964.1	P33991
MCM4	ENST00000262105.6	TSL:1	c.-327_-326insC	upstream_gene	N/A	ENSP00000262105.2	P33991

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

151734

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000508

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000418

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000891

AC:

AN:

179646

Hom.:

AF XY:

0.000105

AC XY:

AN XY:

95578

show subpopulations

African (AFR)

AF:

0.000845

AC:

AN:

3550

American (AMR)

AF:

0.00

AC:

AN:

2768

Ashkenazi Jewish (ASJ)

AF:

0.000177

AC:

AN:

5654

East Asian (EAS)

AF:

0.000115

AC:

AN:

8684

South Asian (SAS)

AF:

0.000213

AC:

AN:

23526

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12216

Middle Eastern (MID)

AF:

0.00

AC:

AN:

828

European-Non Finnish (NFE)

AF:

0.0000538

AC:

AN:

111600

Other (OTH)

AF:

0.00

AC:

AN:

10820

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.422

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000158

AC:

AN:

151854

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.000507

AC:

AN:

41422

American (AMR)

AF:

0.00

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5134

South Asian (SAS)

AF:

0.000418

AC:

AN:

4786

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10562

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67900

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000159

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary immunodeficiency with natural-killer cell deficiency and adrenal insufficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over