19-45759028-C-G

Position:

• chr19-45759028-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001310124.2(MEIOSIN):​c.1163C>G​(p.Thr388Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• 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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24891871).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEIOSIN	NM_001310124.2	c.1163C>G	p.Thr388Ser	missense_variant	10/15	ENST00000457052.3	NP_001297053.1
MEIOSIN	XM_011527571.3	c.1181C>G	p.Thr394Ser	missense_variant	10/15		XP_011525873.1
MEIOSIN	XM_011527573.4	c.1127C>G	p.Thr376Ser	missense_variant	9/14		XP_011525875.1
MEIOSIN	XM_011527574.3	c.1076C>G	p.Thr359Ser	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>G	p.Thr388Ser	missense_variant	10/15	5	NM_001310124.2	ENSP00000402674.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	13
DANN	Benign	0.91
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.31	T
M_CAP	Pathogenic	0.33	D
MetaRNN	Benign	0.25	T
MetaSVM	Pathogenic	0.90	D
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.35
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.38	T
Vest4		0.062
MutPred		0.33		Loss of helix (P = 0.0041);
MVP		0.53
MPC		0.0029
ClinPred		0.55	D
GERP RS		1.3
Varity_R		0.059
gMVP		0.17

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;