Genetic Variant NM_002383.4:c.34C>G (chr16-29806735-C-G) – 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.34C>G(p.Pro12Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000161 in 1,242,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. P12T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

MAZ
NM_002383.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.329

Publications

2 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:

Genome browser will be placed here

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=0.095912814).

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.34C>G	p.Pro12Ala	missense	Exon 1 of 5	NP_002374.2	P56270-1
MAZ	NM_001042539.3		c.34C>G	p.Pro12Ala	missense	Exon 1 of 6	NP_001036004.1	P56270-2
MAZ	NM_001276276.2		c.34C>G	p.Pro12Ala	missense	Exon 1 of 3	NP_001263205.1	P56270-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAZ	ENST00000322945.11	TSL:1 MANE Select	c.34C>G	p.Pro12Ala	missense	Exon 1 of 5	ENSP00000313362.6	P56270-1
MAZ	ENST00000219782.11	TSL:1	c.34C>G	p.Pro12Ala	missense	Exon 1 of 6	ENSP00000219782.6	P56270-2
MAZ	ENST00000545521.5	TSL:1	c.37-72C>G		intron	N/A	ENSP00000443956.1	P56270-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000632

AC:

AN:

158228

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000528

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000161

AC:

AN:

1242904

Hom.:

Cov.:

AF XY:

0.00000162

AC XY:

AN XY:

617456

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000419

AC:

AN:

23890

American (AMR)

AF:

0.00

AC:

AN:

23594

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18802

East Asian (EAS)

AF:

0.00

AC:

AN:

27040

South Asian (SAS)

AF:

0.00

AC:

AN:

65748

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4764

European-Non Finnish (NFE)

AF:

0.00000101

AC:

AN:

988286

Other (OTH)

AF:

0.00

AC:

AN:

47214

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.10

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.71

M_CAP

Benign

0.076

MetaRNN

Benign

0.096

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PhyloP100

-0.33

PrimateAI

Uncertain

0.65

PROVEAN

Benign

0.51

REVEL

Benign

0.048

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.0020

Vest4

0.20

MutPred

0.50

Loss of disorder (P = 0.0394)

MVP

0.20

MPC

0.013

ClinPred

0.097

GERP RS

-0.20

PromoterAI

-0.11

Neutral

(source)

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

3.3

Varity_R

0.078

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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