NM_001321739.2:c.426+522G>A

Variant names:

• chr2-74614442-C-T
• rs363691
• NM_001321739.2:c.426+522G>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.426+522G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,176 control chromosomes in the GnomAD database, including 1,504 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 0.11 (1504 hom., cov: 32)
• Consequence: M1AP NM_001321739.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640
• Publications: 7 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321739.2. 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
	M1AP	NM_001321739.2	MANE Select	c.426+522G>A		intron	N/A	NP_001308668.1	Q8TC57-1
	M1AP	NM_138804.5		c.426+522G>A		intron	N/A	NP_620159.2
	M1AP	NM_001281296.2		c.426+522G>A		intron	N/A	NP_001268225.1	Q8TC57-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	M1AP	ENST00000421985.2	TSL:2 MANE Select	c.426+522G>A		intron	N/A	ENSP00000414882.2	Q8TC57-1
	M1AP	ENST00000290536.9	TSL:1	c.426+522G>A		intron	N/A	ENSP00000290536.5	Q8TC57-1
	M1AP	ENST00000409585.5	TSL:5	c.426+522G>A		intron	N/A	ENSP00000386793.1	Q8TC57-4

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17328 AN: 152058 Hom.: 1504 Cov.: 32

Gnomad AFR AF: 0.0613

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.0857

Gnomad ASJ AF: 0.0943

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.114 AC: 17331 AN: 152176 Hom.: 1504 Cov.: 32 AF XY: 0.119 AC XY: 8882 AN XY: 74394

African (AFR) AF: 0.0612 AC: 2542 AN: 41524

American (AMR) AF: 0.0856 AC: 1310 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0943 AC: 327 AN: 3466

East Asian (EAS) AF: 0.485 AC: 2499 AN: 5152

South Asian (SAS) AF: 0.237 AC: 1141 AN: 4814

European-Finnish (FIN) AF: 0.145 AC: 1540 AN: 10586

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7556 AN: 68014

Other (OTH) AF: 0.114 AC: 241 AN: 2114

Alfa AF: 0.105 Hom.: 1189

Bravo AF: 0.105

Asia WGS AF: 0.338 AC: 1173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.48
PhyloP100		-0.064
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: rs363691; hg19: chr2-74841569;