rs2298695

Variant names:

• chr21-46235113-A-C
• rs2298695
• ENST00000420074.1:n.1607A>C

Your query was ambiguous. Multiple possible variants found:

• chr21-46235113-A-C
• chr21-46235113-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000420074.1(MCM3AP-AS1):​n.1607A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 837,586 control chromosomes in the GnomAD database, including 58,268 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (8733 hom., cov: 33)
  • Exomes 𝑓: 0.37 (49535 hom.)
• Consequence: MCM3AP-AS1 ENST00000420074.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.140
• Publications: 17 publications found

Genes affected

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

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 Gene-Disease associations (from GenCC):

• peripheral neuropathy, autosomal recessive, with or without impaired intellectual development

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 21-46235113-A-C is Benign according to our data. Variant chr21-46235113-A-C is described in ClinVar as Benign. ClinVar VariationId is 1228038.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.394 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000420074.1. 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
	MCM3AP-AS1	NR_002776.4		n.37-5721A>C		intron	N/A
	MCM3AP-AS1	NR_110565.1		n.237+4586A>C		intron	N/A
	MCM3AP-AS1	NR_110566.1		n.37-1111A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MCM3AP-AS1	ENST00000420074.1	TSL:1	n.1607A>C		non_coding_transcript_exon	Exon 2 of 2
	MCM3AP-AS1	ENST00000455567.2	TSL:1	n.72-5721A>C		intron	N/A
	MCM3AP-AS1	ENST00000414659.5	TSL:2	n.237+4586A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49469 AN: 152054 Hom.: 8726 Cov.: 33

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.345

GnomAD4 exome AF: 0.372 AC: 255211 AN: 685414 Hom.: 49535 Cov.: 9 AF XY: 0.373 AC XY: 130611 AN XY: 349776

African (AFR) AF: 0.231 AC: 3894 AN: 16870

American (AMR) AF: 0.249 AC: 4881 AN: 19598

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 5941 AN: 15202

East Asian (EAS) AF: 0.110 AC: 3527 AN: 32062

South Asian (SAS) AF: 0.374 AC: 18490 AN: 49454

European-Finnish (FIN) AF: 0.365 AC: 11664 AN: 31924

Middle Eastern (MID) AF: 0.410 AC: 1008 AN: 2456

European-Non Finnish (NFE) AF: 0.400 AC: 193809 AN: 484306

Other (OTH) AF: 0.358 AC: 11997 AN: 33542

GnomAD4 genome AF: 0.325 AC: 49513 AN: 152172 Hom.: 8733 Cov.: 33 AF XY: 0.321 AC XY: 23874 AN XY: 74412

African (AFR) AF: 0.227 AC: 9443 AN: 41528

American (AMR) AF: 0.281 AC: 4303 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 1347 AN: 3468

East Asian (EAS) AF: 0.116 AC: 600 AN: 5186

South Asian (SAS) AF: 0.350 AC: 1690 AN: 4822

European-Finnish (FIN) AF: 0.359 AC: 3799 AN: 10592

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27051 AN: 67976

Other (OTH) AF: 0.346 AC: 730 AN: 2108

Alfa AF: 0.366 Hom.: 31019

Bravo AF: 0.315

Asia WGS AF: 0.253 AC: 882 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	9.5
DANN	Benign	0.89
PhyloP100		0.14
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

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

Other links and lift over

dbSNP: rs2298695; hg19: chr21-47655027;