Genetic Variant MAZ:p.Arg22Pro (chr16-29806766-G-C) – 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.65G>C(p.Arg22Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000156 in 1,278,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. R22Q) 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: 0.0280

Publications

0 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=0.104558915).

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.65G>C	p.Arg22Pro	missense	Exon 1 of 5	NP_002374.2	P56270-1
MAZ	NM_001042539.3		c.65G>C	p.Arg22Pro	missense	Exon 1 of 6	NP_001036004.1	P56270-2
MAZ	NM_001276276.2		c.65G>C	p.Arg22Pro	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.65G>C	p.Arg22Pro	missense	Exon 1 of 5	ENSP00000313362.6	P56270-1
MAZ	ENST00000219782.11	TSL:1	c.65G>C	p.Arg22Pro	missense	Exon 1 of 6	ENSP00000219782.6	P56270-2
MAZ	ENST00000545521.5	TSL:1	c.37-41G>C		intron	N/A	ENSP00000443956.1	P56270-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000156

AC:

AN:

1278452

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

635496

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24230

American (AMR)

AF:

0.00

AC:

AN:

21438

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19830

East Asian (EAS)

AF:

0.00

AC:

AN:

28050

South Asian (SAS)

AF:

0.0000144

AC:

AN:

69246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46154

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4994

European-Non Finnish (NFE)

AF:

9.86e-7

AC:

AN:

1014634

Other (OTH)

AF:

0.00

AC:

AN:

49876

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

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

0.28

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.12

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.74

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PhyloP100

0.028

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.52

REVEL

Benign

0.11

Sift

Uncertain

0.0070

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.32

MutPred

0.35

Gain of disorder (P = 0.0213)

MVP

0.36

MPC

0.013

ClinPred

0.15

GERP RS

-1.5

PromoterAI

-0.0042

Neutral

(source)

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.2

Varity_R

0.20

gMVP

0.21

Mutation Taster

=94/6

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

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