rs2041975

Variant names:

• chr19-45735297-T-C
• rs2041975
• NM_001310124.2:c.1-80T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001310124.2(MEIOSIN):​c.1-80T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 686,928 control chromosomes in the GnomAD database, including 85,149 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 0.47 (17139 hom., cov: 30)
  • Exomes 𝑓: 0.50 (68010 hom.)
• Consequence: MEIOSIN NM_001310124.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249
• Publications: 17 publications found

Genes affected

MEIOSIN (HGNC:44318): (meiosis initiator) Predicted to enable DNA binding activity and protein dimerization activity. Predicted to be involved in several processes, including activation of meiosis; cellular response to retinoic acid; and gamete generation. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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 = 0.633 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001310124.2. 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
	MEIOSIN	NM_001310124.2	MANE Select	c.1-80T>C		intron	N/A	NP_001297053.1	C9JSJ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEIOSIN	ENST00000457052.3	TSL:5 MANE Select	c.1-80T>C		intron	N/A	ENSP00000402674.3	C9JSJ3
	MEIOSIN	ENST00000926455.1		c.-80T>C		5_prime_UTR	Exon 1 of 14	ENSP00000596514.1

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71199 AN: 151762 Hom.: 17128 Cov.: 30

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.481

GnomAD4 exome AF: 0.497 AC: 265862 AN: 535048 Hom.: 68010 AF XY: 0.500 AC XY: 144698 AN XY: 289630

African (AFR) AF: 0.406 AC: 6288 AN: 15470

American (AMR) AF: 0.665 AC: 22395 AN: 33698

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 7397 AN: 19124

East Asian (EAS) AF: 0.674 AC: 21332 AN: 31670

South Asian (SAS) AF: 0.589 AC: 35857 AN: 60846

European-Finnish (FIN) AF: 0.471 AC: 15416 AN: 32734

Middle Eastern (MID) AF: 0.478 AC: 1671 AN: 3496

European-Non Finnish (NFE) AF: 0.458 AC: 141147 AN: 308252

Other (OTH) AF: 0.483 AC: 14359 AN: 29758

GnomAD4 genome AF: 0.469 AC: 71244 AN: 151880 Hom.: 17139 Cov.: 30 AF XY: 0.476 AC XY: 35305 AN XY: 74194

African (AFR) AF: 0.412 AC: 17085 AN: 41446

American (AMR) AF: 0.595 AC: 9068 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1357 AN: 3472

East Asian (EAS) AF: 0.652 AC: 3356 AN: 5150

South Asian (SAS) AF: 0.601 AC: 2888 AN: 4808

European-Finnish (FIN) AF: 0.452 AC: 4758 AN: 10518

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31291 AN: 67936

Other (OTH) AF: 0.485 AC: 1023 AN: 2110

Alfa AF: 0.465 Hom.: 43645

Bravo AF: 0.477

Asia WGS AF: 0.607 AC: 2113 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	9.5
DANN	Benign	0.71
PhyloP100		-0.25
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: rs2041975; hg19: chr19-46238555;