13-72718960-C-T

Position:

• chr13-72718960-C-T

Variant summary

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

The ENST00000377818.4(MZT1):​c.217G>A​(p.Ala73Thr) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: MZT1 ENST00000377818.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.72

Genes affected

MZT1 (HGNC:33830): (mitotic spindle organizing protein 1) Involved in gamma-tubulin complex localization. Located in centrosome and spindle. 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=0.10035142).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MZT1	NM_001071775.3	c.217G>A	p.Ala73Thr	missense_variant	2/3	ENST00000377818.4	NP_001065243.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MZT1	ENST00000377818.4	c.217G>A	p.Ala73Thr	missense_variant	2/3	1	NM_001071775.3	ENSP00000367049	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

The c.217G>A (p.A73T) alteration is located in exon 2 (coding exon 2) of the MZT1 gene. This alteration results from a G to A substitution at nucleotide position 217, causing the alanine (A) at amino acid position 73 to be replaced by a threonine (T). 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	0.10
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.029
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.98	D
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.073
Sift	Benign	0.19	T
Sift4G	Benign	0.16	T
Polyphen		0.0030	B
Vest4		0.19
MutPred		0.22		Gain of phosphorylation at A73 (P = 0.0512);
MVP		0.22
MPC		0.29
ClinPred		0.95	D
GERP RS		4.8
Varity_R		0.29
gMVP		0.36

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: chr13-73293098;