NM_002383.4:c.436G>A

Variant names:

• chr16-29807221-G-A
• rs930046769
• NM_002383.4:c.436G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002383.4(MAZ):​c.436G>A​(p.Glu146Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E146D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 8.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAZ NM_002383.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.80
• Publications: 1 publications found

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]

ENSG00000259952 (HGNC:):

ACMG classification

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=0.13774961).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAZ	NM_002383.4	MANE Select	c.436G>A	p.Glu146Lys	missense	Exon 2 of 5	NP_002374.2	P56270-1
	MAZ	NM_001042539.3		c.436G>A	p.Glu146Lys	missense	Exon 2 of 6	NP_001036004.1	P56270-2
	MAZ	NM_001276275.2		c.367G>A	p.Glu123Lys	missense	Exon 3 of 6	NP_001263204.1	P56270-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAZ	ENST00000322945.11	TSL:1 MANE Select	c.436G>A	p.Glu146Lys	missense	Exon 2 of 5	ENSP00000313362.6	P56270-1
	MAZ	ENST00000219782.11	TSL:1	c.436G>A	p.Glu146Lys	missense	Exon 2 of 6	ENSP00000219782.6	P56270-2
	MAZ	ENST00000545521.5	TSL:1	c.367G>A	p.Glu123Lys	missense	Exon 3 of 6	ENSP00000443956.1	P56270-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 8.81e-7 AC: 1 AN: 1134510 Hom.: 0 Cov.: 23 AF XY: 0.00000182 AC XY: 1 AN XY: 548274

African (AFR) AF: 0.00 AC: 0 AN: 22562

American (AMR) AF: 0.00 AC: 0 AN: 8696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14798

East Asian (EAS) AF: 0.0000381 AC: 1 AN: 26280

South Asian (SAS) AF: 0.00 AC: 0 AN: 32024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3368

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 946484

Other (OTH) AF: 0.00 AC: 0 AN: 45718

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Benign	0.96
DEOGEN2	Benign	0.11	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.74	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.8
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.052
Sift	Benign	0.23	T
Sift4G	Benign	0.75	T
Polyphen		0.032	B
Vest4		0.31
MutPred		0.36		Gain of ubiquitination at E146 (P = 0.0075)
MVP		0.58
MPC		1.1
ClinPred		0.078	T
GERP RS		-2.0
PromoterAI		0.032	Neutral
Varity_R		0.076
gMVP		0.47
Mutation Taster		=92/8	polymorphism

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

Other links and lift over

dbSNP: rs930046769; hg19: chr16-29818542;