rs725660

Variant names:

• chr19-45759028-C-A
• rs725660
• NM_001310124.2:c.1163C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-45759028-C-A
• chr19-45759028-C-G

Variant summary

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

The NM_001310124.2(MEIOSIN):​c.1163C>A​(p.Thr388Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 702,888 control chromosomes in the GnomAD database, including 40,508 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (8242 hom., cov: 33)
  • Exomes 𝑓: 0.34 (32266 hom.)
• Consequence: MEIOSIN NM_001310124.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.557
• Publications: 28 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 (MetaRNN=0.0031683445).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEIOSIN	NM_001310124.2	c.1163C>A	p.Thr388Asn	missense_variant	Exon 10 of 15	ENST00000457052.3	NP_001297053.1
MEIOSIN	XM_011527571.3	c.1181C>A	p.Thr394Asn	missense_variant	Exon 10 of 15		XP_011525873.1
MEIOSIN	XM_011527573.4	c.1127C>A	p.Thr376Asn	missense_variant	Exon 9 of 14		XP_011525875.1
MEIOSIN	XM_011527574.3	c.1076C>A	p.Thr359Asn	missense_variant	Exon 9 of 14		XP_011525876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEIOSIN	ENST00000457052.3	c.1163C>A	p.Thr388Asn	missense_variant	Exon 10 of 15	5	NM_001310124.2	ENSP00000402674.3

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49532 AN: 152070 Hom.: 8240 Cov.: 33

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.313

GnomAD2 exomes AF: 0.318 AC: 43555 AN: 137060 AF XY: 0.321

Gnomad AFR exome AF: 0.299

Gnomad AMR exome AF: 0.214

Gnomad ASJ exome AF: 0.420

Gnomad EAS exome AF: 0.286

Gnomad FIN exome AF: 0.314

Gnomad NFE exome AF: 0.368

Gnomad OTH exome AF: 0.348

GnomAD4 exome AF: 0.335 AC: 184573 AN: 550700 Hom.: 32266 Cov.: 0 AF XY: 0.336 AC XY: 100212 AN XY: 298136

African (AFR) AF: 0.296 AC: 4673 AN: 15808

American (AMR) AF: 0.221 AC: 7665 AN: 34716

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 8329 AN: 20026

East Asian (EAS) AF: 0.208 AC: 6675 AN: 32104

South Asian (SAS) AF: 0.292 AC: 18354 AN: 62774

European-Finnish (FIN) AF: 0.310 AC: 10427 AN: 33610

Middle Eastern (MID) AF: 0.380 AC: 1550 AN: 4076

European-Non Finnish (NFE) AF: 0.367 AC: 116365 AN: 316970

Other (OTH) AF: 0.344 AC: 10535 AN: 30616

GnomAD4 genome AF: 0.326 AC: 49546 AN: 152188 Hom.: 8242 Cov.: 33 AF XY: 0.319 AC XY: 23761 AN XY: 74408

African (AFR) AF: 0.298 AC: 12374 AN: 41520

American (AMR) AF: 0.260 AC: 3980 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1436 AN: 3470

East Asian (EAS) AF: 0.264 AC: 1365 AN: 5180

South Asian (SAS) AF: 0.285 AC: 1376 AN: 4824

European-Finnish (FIN) AF: 0.321 AC: 3398 AN: 10602

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24579 AN: 67978

Other (OTH) AF: 0.310 AC: 655 AN: 2112

Alfa AF: 0.347 Hom.: 22952

Bravo AF: 0.319

TwinsUK AF: 0.363 AC: 1345

ALSPAC AF: 0.354 AC: 1364

ExAC AF: 0.281 AC: 5316

Asia WGS AF: 0.281 AC: 977 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.43	T
MetaRNN	Benign	0.0032	T
MetaSVM	Benign	-1.4	T
PhyloP100		0.56
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.53
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.077	T
Vest4		0.10
MPC		0.0022
ClinPred		0.033	T
GERP RS		1.3
Varity_R		0.071
gMVP		0.41
Mutation Taster		=96/4	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: rs725660; hg19: chr19-46262286; COSMIC: COSV71837243;