rs725660

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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. 10/16 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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MEIOSIN	NM_001310124.2	c.1163C>A	p.Thr388Asn	missense_variant	10/15	ENST00000457052.3	NP_001297053.1
MEIOSIN	XM_011527571.3	c.1181C>A	p.Thr394Asn	missense_variant	10/15		XP_011525873.1
MEIOSIN	XM_011527573.4	c.1127C>A	p.Thr376Asn	missense_variant	9/14		XP_011525875.1
MEIOSIN	XM_011527574.3	c.1076C>A	p.Thr359Asn	missense_variant	9/14		XP_011525876.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEIOSIN	ENST00000457052.3	c.1163C>A	p.Thr388Asn	missense_variant	10/15	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

GnomAD3 exomes AF: 0.318 AC: 43555 AN: 137060 Hom.: 7326 AF XY: 0.321 AC XY: 23919 AN XY: 74516

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 SAS exome AF: 0.288

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

Gnomad4 AFR exome AF: 0.296

Gnomad4 AMR exome AF: 0.221

Gnomad4 ASJ exome AF: 0.416

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.292

Gnomad4 FIN exome AF: 0.310

Gnomad4 NFE exome AF: 0.367

Gnomad4 OTH exome AF: 0.344

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

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.414

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.310

Alfa AF: 0.351 Hom.: 9331

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
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs725660; hg19: chr19-46262286; COSMIC: COSV71837243;