Variant 13-72727595-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001071775.3(MZT1):c.8G>C(p.Ser3Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000788 in 1,599,618 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 35)

Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

MZT1
NM_001071775.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.60

Variant links:

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]

MZT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0057528615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MZT1	NM_001071775.3 linkuse as main transcript	c.8G>C	p.Ser3Thr	missense_variant	1/3	ENST00000377818.4	NP_001065243.1	Q08AG7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MZT1	ENST00000377818.4 linkuse as main transcript	c.8G>C	p.Ser3Thr	missense_variant	1/3	1	NM_001071775.3	ENSP00000367049.3		Q08AG7

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000737

AC:

AN:

217106

Hom.:

AF XY:

0.0000673

AC XY:

AN XY:

118886

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000626

Gnomad ASJ exome

AF:

0.000760

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000348

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000641

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000650

AC:

AN:

1447266

Hom.:

Cov.:

AF XY:

0.0000765

AC XY:

AN XY:

719012

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.0000935

Gnomad4 ASJ exome

AF:

0.000700

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000236

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000471

Gnomad4 OTH exome

AF:

0.000184

GnomAD4 genome

AF:

0.000210

AC:

AN:

152352

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.000317

ExAC

AF:

0.0000671

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2022

The c.8G>C (p.S3T) alteration is located in exon 1 (coding exon 1) of the MZT1 gene. This alteration results from a G to C substitution at nucleotide position 8, causing the serine (S) at amino acid position 3 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

0.13

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.011

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.37

M_CAP

Benign

0.052

MetaRNN

Benign

0.0058

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.41

REVEL

Benign

0.039

Sift

Benign

0.39

Sift4G

Benign

0.069

Polyphen

0.23

Vest4

0.41

MutPred

0.20

Loss of phosphorylation at S3 (P = 0.0343);

MVP

0.36

MPC

0.26

ClinPred

0.20

GERP RS

3.1

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.055

gMVP

0.58

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over