19-45759027-A-T

Variant names:

• chr19-45759027-A-T
• NM_001310124.2:c.1162A>T
• MEIOSIN p.Thr388Ser

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001310124.2(MEIOSIN):​c.1162A>T​(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. 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: 2.31
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4086543).

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.1162A>T	p.Thr388Ser	missense	Exon 10 of 15	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.1162A>T	p.Thr388Ser	missense	Exon 10 of 15	ENSP00000402674.3	C9JSJ3
	MEIOSIN	ENST00000926455.1		c.1162A>T	p.Thr388Ser	missense	Exon 9 of 14	ENSP00000596514.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.024	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.31	T
M_CAP	Pathogenic	0.69	D
MetaRNN	Benign	0.41	T
MetaSVM	Pathogenic	1.2	D
PhyloP100		2.3
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.47
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.38	T
Varity_R		0.068
gMVP		0.17
Mutation Taster		=90/10	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-46262285;