Variant 16-29807135-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002383.4(MAZ):c.350C>T(p.Ala117Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 1,039,630 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000067 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000045 ( 0 hom. )

Consequence

MAZ
NM_002383.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0710

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:

(HGNC:):

links:

Genome browser will be placed here

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=0.10050598).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAZ	NM_002383.4 linkuse as main transcript	c.350C>T	p.Ala117Val	missense_variant	2/5	ENST00000322945.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAZ	ENST00000322945.11 linkuse as main transcript	c.350C>T	p.Ala117Val	missense_variant	2/5	1	NM_002383.4		P56270-1
	ENST00000566537.1 linkuse as main transcript	n.502+96G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00000674

AC:

AN:

148406

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000449

AC:

AN:

891224

Hom.:

Cov.:

AF XY:

0.00000470

AC XY:

AN XY:

425698

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:

0.00000515

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000674

AC:

AN:

148406

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72292

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000150

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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

May 22, 2023

The c.350C>T (p.A117V) alteration is located in exon 2 (coding exon 2) of the MAZ gene. This alteration results from a C to T substitution at nucleotide position 350, causing the alanine (A) at amino acid position 117 to be replaced by a valine (V). 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

0.14

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.13

.;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.66

T;T;T

M_CAP

Benign

0.067

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N;N

MutationTaster

Benign

0.92

D;D;D;N;N;N

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.44

N;N;N

REVEL

Benign

0.031

Sift

Benign

0.043

D;D;D

Sift4G

Benign

0.58

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.25

MutPred

0.40

.;Gain of catalytic residue at A117 (P = 0.002);Gain of catalytic residue at A117 (P = 0.002);

MVP

0.39

MPC

0.96

ClinPred

0.038

GERP RS

-0.0071

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.049

gMVP

0.40

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