Genetic Variant ENST00000219782.11:c.1460C>T (chr16-29809720-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000219782.11(MAZ):c.1460C>T(p.Pro487Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000611 in 1,473,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000061 ( 0 hom. )

Consequence

MAZ
ENST00000219782.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51

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:

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

MVP-DT links:

ENSG00000280607 (HGNC:):

ENSG00000280607 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.23268735).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000219782.11. 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.1280-357C>T		intron	N/A	NP_002374.2	P56270-1
MAZ	NM_001042539.3		c.1460C>T	p.Pro487Leu	missense	Exon 5 of 6	NP_001036004.1	P56270-2
MAZ	NM_001276275.2		c.1211-357C>T		intron	N/A	NP_001263204.1	P56270-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MAZ	ENST00000219782.11	TSL:1	c.1460C>T	p.Pro487Leu	missense	Exon 5 of 6	ENSP00000219782.6	P56270-2
MAZ	ENST00000322945.11	TSL:1 MANE Select	c.1280-357C>T		intron	N/A	ENSP00000313362.6	P56270-1
MAZ	ENST00000545521.5	TSL:1	c.1211-357C>T		intron	N/A	ENSP00000443956.1	P56270-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000954

AC:

AN:

104782

AF XY:

0.0000173

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000940

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000606

AC:

AN:

1321216

Hom.:

Cov.:

AF XY:

0.00000465

AC XY:

AN XY:

645710

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29376

American (AMR)

AF:

0.00

AC:

AN:

26152

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20062

East Asian (EAS)

AF:

0.0000278

AC:

AN:

35964

South Asian (SAS)

AF:

0.00

AC:

AN:

69692

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35978

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3838

European-Non Finnish (NFE)

AF:

0.00000670

AC:

AN:

1045532

Other (OTH)

AF:

0.00

AC:

AN:

54622

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.638

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:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74348

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

41458

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2092

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 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: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.68

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.0

PhyloP100

1.5

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.41

REVEL

Benign

0.075

Sift

Uncertain

0.014

Sift4G

Pathogenic

0.0

Vest4

0.53

MutPred

0.34

Loss of loop (P = 0.0389)

MVP

0.28

MPC

0.98

ClinPred

0.88

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

gMVP

0.33

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