2-130190486-G-T

Variant names:

• chr2-130190486-G-T
• rs754224613
• NM_025029.5:c.337G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025029.5(MZT2B):​c.337G>T​(p.Ala113Ser) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A113T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MZT2B NM_025029.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 0 publications found

Genes affected

MZT2B (HGNC:25886): (mitotic spindle organizing protein 2B) Located in cytosol; microtubule cytoskeleton; and nucleoplasm. Part of gamma-tubulin large complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055472255).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025029.5. 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
	MZT2B	NM_025029.5	MANE Select	c.337G>T	p.Ala113Ser	missense	Exon 3 of 3	NP_079305.2
	MZT2B	NM_001330282.2		c.517G>T	p.Ala173Ser	missense	Exon 4 of 4	NP_001317211.1	B8ZZ87
	MZT2B	NM_001330284.2		c.188G>T	p.Arg63Leu	missense	Exon 2 of 2	NP_001317213.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MZT2B	ENST00000281871.11	TSL:1 MANE Select	c.337G>T	p.Ala113Ser	missense	Exon 3 of 3	ENSP00000281871.7	Q6NZ67
	MZT2B	ENST00000480182.1	TSL:1	n.239G>T		non_coding_transcript_exon	Exon 2 of 2
	MZT2B	ENST00000409255.1	TSL:5	c.517G>T	p.Ala173Ser	missense	Exon 4 of 4	ENSP00000386419.1	B8ZZ87

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.0030
DANN	Benign	0.77
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.55	N
PhyloP100		-1.1
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	0.43	N
REVEL	Benign	0.019
Sift	Benign	0.64	T
Sift4G	Benign	0.74	T
Polyphen		0.0050	B
Vest4		0.076
MutPred		0.17		Gain of loop (P = 0.0166)
MVP		0.068
MPC		0.10
ClinPred		0.033	T
GERP RS		-5.8
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.037
gMVP		0.096
Mutation Taster		=95/5	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

Other links and lift over

dbSNP: rs754224613; hg19: chr2-130948059;