rs2839186

Positions:

• chr21-46270154-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MCM3AP	NM_003906.5	c.2628+247G>A		intron_variant		ENST00000291688.6
MCM3AP	XM_005261203.5	c.2628+247G>A		intron_variant
MCM3AP	XM_005261204.6	c.2628+247G>A		intron_variant
MCM3AP	XM_005261205.5	c.2628+247G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MCM3AP	ENST00000291688.6	c.2628+247G>A		intron_variant		1	NM_003906.5	P1
MCM3AP	ENST00000397708.1	c.2628+247G>A		intron_variant		5		P1

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

Gnomad4 AFR exome AF: 0.317

Gnomad4 AMR exome AF: 0.503

Gnomad4 ASJ exome AF: 0.470

Gnomad4 EAS exome AF: 0.223

Gnomad4 SAS exome AF: 0.392

Gnomad4 FIN exome AF: 0.474

Gnomad4 NFE exome AF: 0.456

Gnomad4 OTH exome AF: 0.438

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

Gnomad4 AFR AF: 0.326

Gnomad4 AMR AF: 0.482

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.406

Alfa AF: 0.449 Hom.: 10168

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

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

Other links and lift over

dbSNP: rs2839186; hg19: chr21-47690068;