Genetic Variant MAZ:p.Ala445Ala (chr16-29810132-A-G) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_002383.4(MAZ):c.1335A>G(p.Ala445Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000995 in 1,607,766 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00075 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 2 hom. )

Consequence

MAZ
NM_002383.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.12

Publications

3 publications found

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:

ENSG00000280607 (HGNC:):

ENSG00000280607 links:

MVP-DT (HGNC:56029): (MVP divergent transcript)

MVP-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040216744).

BP6

Variant 16-29810132-A-G is Benign according to our data. Variant chr16-29810132-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2646369.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.12 with no splicing effect.

BS2

High AC in GnomAd4 at 114 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAZ	NM_002383.4 link	c.1335A>G	p.Ala445Ala	synonymous_variant	Exon 5 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.1335A>G	p.Ala445Ala	synonymous_variant	Exon 5 of 5	1	NM_002383.4	ENSP00000313362.6		P56270-1

Frequencies

GnomAD3 genomes

AF:

0.000754

AC:

114

AN:

151270

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000682

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00273

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000989

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000839

AC:

202

AN:

240634

AF XY:

0.000703

show subpopulations

Gnomad AFR exome

AF:

0.000856

Gnomad AMR exome

AF:

0.000234

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00276

Gnomad FIN exome

AF:

0.0000953

Gnomad NFE exome

AF:

0.00113

Gnomad OTH exome

AF:

0.000513

GnomAD4 exome

AF:

0.00102

AC:

1485

AN:

1456376

Hom.:

Cov.:

AF XY:

0.000944

AC XY:

684

AN XY:

724486

show subpopulations

African (AFR)

AF:

0.000570

AC:

AN:

33348

American (AMR)

AF:

0.000247

AC:

AN:

44540

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26060

East Asian (EAS)

AF:

0.00373

AC:

148

AN:

39630

South Asian (SAS)

AF:

0.000186

AC:

AN:

86120

European-Finnish (FIN)

AF:

0.0000958

AC:

AN:

52212

Middle Eastern (MID)

AF:

0.000531

AC:

AN:

5654

European-Non Finnish (NFE)

AF:

0.00113

AC:

1251

AN:

1108706

Other (OTH)

AF:

0.000532

AC:

AN:

60106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

178

267

356

445

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000753

AC:

114

AN:

151390

Hom.:

Cov.:

AF XY:

0.000689

AC XY:

AN XY:

74006

show subpopulations

African (AFR)

AF:

0.000680

AC:

AN:

41184

American (AMR)

AF:

0.000263

AC:

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00274

AC:

AN:

5108

South Asian (SAS)

AF:

0.000209

AC:

AN:

4782

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000989

AC:

AN:

67720

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00106

Hom.:

ESP6500AA

AF:

0.000519

AC:

ESP6500EA

AF:

0.000880

AC:

ExAC

AF:

0.000975

AC:

117

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

MAZ: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

0.076

(source)

DANN

Benign

0.57

FATHMM_MKL

Benign

0.0085

LIST_S2

Benign

0.20

T;T

M_CAP

Benign

0.0067

MetaRNN

Benign

0.0040

T;T

PhyloP100

-2.1

PROVEAN

Benign

0.71

.;N

Sift

Pathogenic

0.0

.;D

Sift4G

Benign

0.22

T;T

Vest4

0.087

MVP

0.30

GERP RS

-6.5

Mutation Taster

=93/7

polymorphism

(source)

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

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16-29810132-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over