NM_001321739.2:c.596-5862G>A

Variant names:

• chr2-74587709-C-T
• rs363685
• NM_001321739.2:c.596-5862G>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.596-5862G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0834 in 152,082 control chromosomes in the GnomAD database, including 1,489 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 0.083 (1489 hom., cov: 32)
• Consequence: M1AP NM_001321739.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.23
• Publications: 3 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 = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
M1AP	NM_001321739.2	c.596-5862G>A		intron_variant	Intron 4 of 10	ENST00000421985.2	NP_001308668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
M1AP	ENST00000421985.2	c.596-5862G>A		intron_variant	Intron 4 of 10	2	NM_001321739.2	ENSP00000414882.2

Frequencies

GnomAD3 genomes AF: 0.0833 AC: 12653 AN: 151964 Hom.: 1482 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0360

Gnomad ASJ AF: 0.0683

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0261

Gnomad FIN AF: 0.00227

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.0642

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0834 AC: 12687 AN: 152082 Hom.: 1489 Cov.: 32 AF XY: 0.0795 AC XY: 5908 AN XY: 74360

African (AFR) AF: 0.263 AC: 10909 AN: 41404

American (AMR) AF: 0.0359 AC: 549 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0683 AC: 237 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5180

South Asian (SAS) AF: 0.0261 AC: 126 AN: 4822

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: 0.0102 AC: 695 AN: 68006

Other (OTH) AF: 0.0635 AC: 134 AN: 2110

Alfa AF: 0.0160 Hom.: 30

Bravo AF: 0.0949

Asia WGS AF: 0.0360 AC: 124 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	0.080
DANN	Benign	0.56
PhyloP100		-3.2
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: rs363685; hg19: chr2-74814836;