chr2-130190508-C-G

Variant names:

• chr2-130190508-C-G
• NM_025029.5:c.359C>G

Variant summary

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

The NM_025029.5(MZT2B):​c.359C>G​(p.Ala120Gly) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: MZT2B NM_025029.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.170

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

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=0.07488966).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MZT2B	NM_025029.5	c.359C>G	p.Ala120Gly	missense_variant	Exon 3 of 3	ENST00000281871.11	NP_079305.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MZT2B	ENST00000281871.11	c.359C>G	p.Ala120Gly	missense_variant	Exon 3 of 3	1	NM_025029.5	ENSP00000281871.7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.359C>G (p.A120G) alteration is located in exon 3 (coding exon 3) of the MZT2B gene. This alteration results from a C to G substitution at nucleotide position 359, causing the alanine (A) at amino acid position 120 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	4.3
DANN	Benign	0.88
DEOGEN2	Benign	0.022	.;T;.
Eigen	Benign	-0.90
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.63	T;T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.075	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.71	.;N;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.026
Sift	Benign	0.18	T;T;T
Sift4G	Benign	0.37	T;T;T
Polyphen		0.42	.;B;.
Vest4		0.090, 0.10
MutPred		0.26		.;Loss of helix (P = 0.0041);.;
MVP		0.068
MPC		0.11
ClinPred		0.16	T
GERP RS		0.19
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
Varity_R		0.044
gMVP		0.099

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-130948081;