Genetic Variant MAZ:p.Pro80Ser (chr16-29807023-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002383.4(MAZ):c.238C>T(p.Pro80Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000298 in 1,006,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P80A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000012 ( 0 hom. )

Consequence

MAZ
NM_002383.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.882

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08050075).

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.238C>T	p.Pro80Ser	missense	Exon 2 of 5	NP_002374.2	P56270-1
MAZ	NM_001042539.3		c.238C>T	p.Pro80Ser	missense	Exon 2 of 6	NP_001036004.1	P56270-2
MAZ	NM_001276275.2		c.169C>T	p.Pro57Ser	missense	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.238C>T	p.Pro80Ser	missense	Exon 2 of 5	ENSP00000313362.6	P56270-1
MAZ	ENST00000219782.11	TSL:1	c.238C>T	p.Pro80Ser	missense	Exon 2 of 6	ENSP00000219782.6	P56270-2
MAZ	ENST00000545521.5	TSL:1	c.169C>T	p.Pro57Ser	missense	Exon 3 of 6	ENSP00000443956.1	P56270-3

Frequencies

GnomAD3 genomes

AF:

0.0000137

AC:

AN:

146458

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000491

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:

0.00000116

AC:

AN:

860382

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

401864

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

16190

American (AMR)

AF:

0.00

AC:

AN:

1890

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5610

East Asian (EAS)

AF:

0.00

AC:

AN:

4550

South Asian (SAS)

AF:

0.00

AC:

AN:

17756

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2524

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1738

European-Non Finnish (NFE)

AF:

0.00000128

AC:

AN:

781396

Other (OTH)

AF:

0.00

AC:

AN:

28728

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000137

AC:

AN:

146458

Hom.:

Cov.:

AF XY:

0.0000140

AC XY:

AN XY:

71236

show subpopulations

African (AFR)

AF:

0.0000491

AC:

AN:

40744

American (AMR)

AF:

0.00

AC:

AN:

14766

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3390

East Asian (EAS)

AF:

0.00

AC:

AN:

5030

South Asian (SAS)

AF:

0.00

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8638

Middle Eastern (MID)

AF:

0.00

AC:

AN:

308

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65866

Other (OTH)

AF:

0.00

AC:

AN:

2008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.69

M_CAP

Benign

0.048

MetaRNN

Benign

0.081

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

PhyloP100

0.88

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

0.040

REVEL

Benign

0.026

Sift

Benign

0.14

Sift4G

Benign

0.27

Polyphen

0.0030

Vest4

0.19

MutPred

0.21

Gain of glycosylation at P80 (P = 0.0338)

MVP

0.27

MPC

0.97

ClinPred

0.079

GERP RS

1.3

PromoterAI

0.038

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.3

Varity_R

0.053

gMVP

0.43

Mutation Taster

=79/21

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over