Genetic Variant MAZ:p.Glu146* (chr16-29807221-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002383.4(MAZ):c.436G>T(p.Glu146*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000133 in 150,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

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

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MAZ
NM_002383.4 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.80

Publications

1 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:

ENSG00000259952 (HGNC:):

ENSG00000259952 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002383.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAZ	NM_002383.4	MANE Select	c.436G>T	p.Glu146*	stop_gained	Exon 2 of 5	NP_002374.2	P56270-1
MAZ	NM_001042539.3		c.436G>T	p.Glu146*	stop_gained	Exon 2 of 6	NP_001036004.1	P56270-2
MAZ	NM_001276275.2		c.367G>T	p.Glu123*	stop_gained	Exon 3 of 6	NP_001263204.1	P56270-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAZ	ENST00000322945.11	TSL:1 MANE Select	c.436G>T	p.Glu146*	stop_gained	Exon 2 of 5	ENSP00000313362.6	P56270-1
MAZ	ENST00000219782.11	TSL:1	c.436G>T	p.Glu146*	stop_gained	Exon 2 of 6	ENSP00000219782.6	P56270-2
MAZ	ENST00000545521.5	TSL:1	c.367G>T	p.Glu123*	stop_gained	Exon 3 of 6	ENSP00000443956.1	P56270-3

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

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1134510

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

548274

African (AFR)

AF:

0.00

AC:

AN:

22562

American (AMR)

AF:

0.00

AC:

AN:

8696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14798

East Asian (EAS)

AF:

0.00

AC:

AN:

26280

South Asian (SAS)

AF:

0.00

AC:

AN:

32024

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3368

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

946484

Other (OTH)

AF:

0.00

AC:

AN:

45718

GnomAD4 genome

AF:

0.0000133

AC:

AN:

150440

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73436

show subpopulations

African (AFR)

AF:

0.0000486

AC:

AN:

41114

American (AMR)

AF:

0.00

AC:

AN:

15130

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5130

South Asian (SAS)

AF:

0.00

AC:

AN:

4800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10074

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67440

Other (OTH)

AF:

0.00

AC:

AN:

2068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.093

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.17

PhyloP100

1.8

Vest4

0.26

GERP RS

-2.0

PromoterAI

0.28

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over