dbSNP rs2839186: MCM3AP:c.2628+247G>A (chr21-46270154-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003906.5(MCM3AP):c.2628+247G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 348,574 control chromosomes in the GnomAD database, including 32,694 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 0.42 ( 13639 hom., cov: 33)

Exomes 𝑓: 0.43 ( 19055 hom. )

Consequence

MCM3AP
NM_003906.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.126

Publications

40 publications found

Variant links:

Genes affected

MCM3AP (HGNC:6946): (minichromosome maintenance complex component 3 associated protein) The minichromosome maintenance protein 3 (MCM3) is one of the MCM proteins essential for the initiation of DNA replication. The protein encoded by this gene is a MCM3 binding protein. It was reported to have phosphorylation-dependent DNA-primase activity, which was up-regulated in antigen immunization induced germinal center. This protein was demonstrated to be an acetyltransferase that acetylates MCM3 and plays a role in DNA replication. The mutagenesis of a nuclear localization signal of MCM3 affects the binding of this protein with MCM3, suggesting that this protein may also facilitate MCM3 nuclear localization. This gene is expressed in the brain or in neuronal tissue. An allelic variant encoding amino acid Lys at 915, instead of conserved Glu, has been identified in patients with mild intellectual disability. [provided by RefSeq, Jan 2014]

MCM3AP links:

MCM3AP-AS1 (HGNC:16417): (MCM3AP antisense RNA 1)

MCM3AP-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MCM3AP	NM_003906.5 link	c.2628+247G>A	intron_variant	Intron 9 of 27	ENST00000291688.6	NP_003897.2	O60318-1
MCM3AP	XM_005261203.5 link	c.2628+247G>A	intron_variant	Intron 10 of 28		XP_005261260.1	O60318-1
MCM3AP	XM_005261204.6 link	c.2628+247G>A	intron_variant	Intron 10 of 28		XP_005261261.1	O60318-1
MCM3AP	XM_005261205.5 link	c.2628+247G>A	intron_variant	Intron 10 of 28		XP_005261262.1	O60318-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MCM3AP	ENST00000291688.6 link	c.2628+247G>A		intron_variant	Intron 9 of 27	1	NM_003906.5	ENSP00000291688.1		O60318-1

Frequencies

GnomAD3 genomes

AF:

0.417

AC:

63305

AN:

151936

Hom.:

13632

Cov.:

show subpopulations

Gnomad AFR

AF:

0.326

Gnomad AMI

AF:

0.271

Gnomad AMR

AF:

0.482

Gnomad ASJ

AF:

0.464

Gnomad EAS

AF:

0.284

Gnomad SAS

AF:

0.385

Gnomad FIN

AF:

0.488

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.458

Gnomad OTH

AF:

0.409

GnomAD4 exome

AF:

0.432

AC:

84812

AN:

196520

Hom.:

19055

AF XY:

0.433

AC XY:

43171

AN XY:

99678

show subpopulations

African (AFR)

AF:

0.317

AC:

1980

AN:

6244

American (AMR)

AF:

0.503

AC:

2962

AN:

5884

Ashkenazi Jewish (ASJ)

AF:

0.470

AC:

3608

AN:

7680

East Asian (EAS)

AF:

0.223

AC:

3918

AN:

17562

South Asian (SAS)

AF:

0.392

AC:

1475

AN:

3760

European-Finnish (FIN)

AF:

0.474

AC:

6662

AN:

14046

Middle Eastern (MID)

AF:

0.417

AC:

435

AN:

1042

European-Non Finnish (NFE)

AF:

0.456

AC:

57876

AN:

126850

Other (OTH)

AF:

0.438

AC:

5896

AN:

13452

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

2193

4385

6578

8770

10963

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

242

484

726

968

1210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.417

AC:

63331

AN:

152054

Hom.:

13639

Cov.:

AF XY:

0.418

AC XY:

31063

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.326

AC:

13509

AN:

41482

American (AMR)

AF:

0.482

AC:

7360

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.464

AC:

1609

AN:

3466

East Asian (EAS)

AF:

0.283

AC:

1467

AN:

5176

South Asian (SAS)

AF:

0.384

AC:

1851

AN:

4822

European-Finnish (FIN)

AF:

0.488

AC:

5149

AN:

10560

Middle Eastern (MID)

AF:

0.449

AC:

132

AN:

294

European-Non Finnish (NFE)

AF:

0.458

AC:

31150

AN:

67962

Other (OTH)

AF:

0.406

AC:

857

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1921

3843

5764

7686

9607

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

600

1200

1800

2400

3000

<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:

0.440

Hom.:

35621

Bravo

AF:

0.413

Asia WGS

AF:

0.324

AC:

1129

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.9

(source)

DANN

Benign

0.50

PhyloP100

0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over