rs363693

Positions:

• chr2-74615802-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321739.2(M1AP):​c.241-653G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0812 in 152,280 control chromosomes in the GnomAD database, including 1,405 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 0.081 (1405 hom., cov: 32)
  • Exomes 𝑓: 0.010 (0 hom.)
• Consequence: M1AP NM_001321739.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163

Genes affected

M1AP (HGNC:25183): (meiosis 1 associated protein) This gene encodes a protein that is likely to function in progression of meiosis. A similar protein in mouse plays a role in gametogenesis in both sexes. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

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 (AFR) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
M1AP	NM_001321739.2	c.241-653G>A		intron_variant		ENST00000421985.2	NP_001308668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
M1AP	ENST00000421985.2	c.241-653G>A		intron_variant		2	NM_001321739.2	ENSP00000414882	P4

Frequencies

GnomAD3 genomes AF: 0.0811 AC: 12323 AN: 151968 Hom.: 1398 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0355

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0272

Gnomad FIN AF: 0.00227

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0101

Gnomad OTH AF: 0.0627

GnomAD4 exome AF: 0.0103 AC: 2 AN: 194 Hom.: 0 Cov.: 0 AF XY: 0.00926 AC XY: 1 AN XY: 108

Gnomad4 AMR exome AF: 0.0333

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00658

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0813 AC: 12357 AN: 152086 Hom.: 1405 Cov.: 32 AF XY: 0.0774 AC XY: 5756 AN XY: 74348

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.0354

Gnomad4 ASJ AF: 0.0683

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0272

Gnomad4 FIN AF: 0.00227

Gnomad4 NFE AF: 0.0101

Gnomad4 OTH AF: 0.0621

Alfa AF: 0.0560 Hom.: 127

Bravo AF: 0.0926

Asia WGS AF: 0.0350 AC: 123 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	5.6
DANN	Benign	0.58

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: rs363693; hg19: chr2-74842929;