chr21-46270154-C-T

Variant names:

• chr21-46270154-C-T
• rs2839186
• NM_003906.5:c.2628+247G>A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126
• Publications: 40 publications found

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

ACMG classification

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63305 AN: 151936 Hom.: 13632 Cov.: 33

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

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

GnomAD4 genome AF: 0.417 AC: 63331 AN: 152054 Hom.: 13639 Cov.: 33 AF XY: 0.418 AC XY: 31063 AN XY: 74330

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

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
DANN	Benign	0.50
PhyloP100		0.13
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: rs2839186; hg19: chr21-47690068;