rs363693

Variant names:

• chr2-74615802-C-T
• rs363693
• NM_001321739.2:c.241-653G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

M1AP Gene-Disease associations (from GenCC):

• spermatogenic failure 48

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
M1AP	NM_001321739.2	c.241-653G>A		intron_variant	Intron 2 of 10	ENST00000421985.2	NP_001308668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
M1AP	ENST00000421985.2	c.241-653G>A		intron_variant	Intron 2 of 10	2	NM_001321739.2	ENSP00000414882.2

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.0333 AC: 1 AN: 30

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 8

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00658 AC: 1 AN: 152

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.256 AC: 10594 AN: 41434

American (AMR) AF: 0.0354 AC: 541 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0683 AC: 237 AN: 3468

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.0272 AC: 131 AN: 4816

European-Finnish (FIN) AF: 0.00227 AC: 24 AN: 10594

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0101 AC: 687 AN: 67998

Other (OTH) AF: 0.0621 AC: 131 AN: 2110

Alfa AF: 0.0627 Hom.: 152

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
PhyloP100		0.16
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: rs363693; hg19: chr2-74842929;