Variant 16-29806711-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002383.4(MAZ):c.10G>C(p.Val4Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000439 in 1,320,514 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.000061 ( 1 hom., cov: 30)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

MAZ
NM_002383.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.272

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03986177).

BS2

High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAZ	NM_002383.4 link	c.10G>C	p.Val4Leu	missense_variant	1/5	ENST00000322945.11	NP_002374.2	P56270-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAZ	ENST00000322945.11 link	c.10G>C	p.Val4Leu	missense_variant	1/5	1	NM_002383.4	ENSP00000313362.6		P56270-1

Frequencies

GnomAD3 genomes

AF:

0.0000614

AC:

AN:

146578

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000269

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00333

Gnomad NFE

AF:

0.0000303

Gnomad OTH

AF:

0.000986

GnomAD3 exomes

AF:

0.0000763

AC:

AN:

144132

Hom.:

AF XY:

0.0000719

AC XY:

AN XY:

83454

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000527

Gnomad ASJ exome

AF:

0.000167

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000293

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000417

AC:

AN:

1173848

Hom.:

Cov.:

AF XY:

0.0000448

AC XY:

AN XY:

580372

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000339

Gnomad4 ASJ exome

AF:

0.0000621

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000327

Gnomad4 OTH exome

AF:

0.000162

GnomAD4 genome

AF:

0.0000614

AC:

AN:

146666

Hom.:

Cov.:

AF XY:

0.0000560

AC XY:

AN XY:

71478

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000269

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000303

Gnomad4 OTH

AF:

0.000977

Bravo

AF:

0.0000831

ExAC

AF:

0.0000674

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

Aug 15, 2024

The c.10G>C (p.V4L) alteration is located in exon 1 (coding exon 1) of the MAZ gene. This alteration results from a G to C substitution at nucleotide position 10, causing the valine (V) at amino acid position 4 to be replaced by a leucine (L). 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

0.20

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.11

T;.;.;.;.

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.73

T;T;T;T;T

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.040

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

N;N;.;.;N

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.040

N;N;.;N;N

REVEL

Benign

0.038

Sift

Pathogenic

0.0

D;D;.;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

0.0010

B;.;.;.;.

Vest4

0.25

MutPred

0.26

Gain of disorder (P = 0.0963);Gain of disorder (P = 0.0963);Gain of disorder (P = 0.0963);Gain of disorder (P = 0.0963);Gain of disorder (P = 0.0963);

MVP

0.10

MPC

0.013

ClinPred

0.10

GERP RS

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.18

gMVP

0.075

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