Genetic Variant MAZ:p.Glu146Gln (chr16-29807221-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002383.4(MAZ):c.436G>C(p.Glu146Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000233 in 1,284,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 8.8e-7 ( 0 hom. )

Consequence

MAZ
NM_002383.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.80

Variant links:

Genes affected

MAZ (HGNC:6914): (MYC associated zinc finger protein) Enables DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in several processes, including regulation of gene expression; regulation of signal transduction; and transcription by RNA polymerase II. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

MAZ links:

ENSG00000259952 (HGNC:):

ENSG00000259952 links:

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ACMG classification

Classification made for transcript

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=0.10979617).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAZ	NM_002383.4 link	c.436G>C	p.Glu146Gln	missense_variant	Exon 2 of 5	ENST00000322945.11	NP_002374.2	P56270-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAZ	ENST00000322945.11 link	c.436G>C	p.Glu146Gln	missense_variant	Exon 2 of 5	1	NM_002383.4	ENSP00000313362.6		P56270-1

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150440

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000486

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

8.81e-7

AC:

AN:

1134510

Hom.:

Cov.:

AF XY:

0.00000182

AC XY:

AN XY:

548274

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000106

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150440

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73436

show subpopulations

Gnomad4 AFR

AF:

0.0000486

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.11

.;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.66

T;T;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

.;N;N

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

0.090

N;N;N

REVEL

Benign

0.018

Sift

Benign

0.21

T;T;T

Sift4G

Benign

0.48

T;T;T

Polyphen

0.0010

.;B;.

Vest4

0.20

MutPred

0.23

.;Gain of catalytic residue at E146 (P = 0.0997);Gain of catalytic residue at E146 (P = 0.0997);

MVP

0.30

MPC

0.95

ClinPred

0.070

GERP RS

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.46

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over