NM_002383.4:c.65G>A

Variant names:

• chr16-29806766-G-A
• rs755933237
• NM_002383.4:c.65G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002383.4(MAZ):​c.65G>A​(p.Arg22Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000491 in 1,426,224 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000039 (0 hom.)
• Consequence: MAZ NM_002383.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0280
• Publications: 0 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.059981912).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

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.65G>A	p.Arg22Gln	missense	Exon 1 of 5	NP_002374.2	P56270-1
	MAZ	NM_001042539.3		c.65G>A	p.Arg22Gln	missense	Exon 1 of 6	NP_001036004.1	P56270-2
	MAZ	NM_001276276.2		c.65G>A	p.Arg22Gln	missense	Exon 1 of 3	NP_001263205.1	P56270-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAZ	ENST00000322945.11	TSL:1 MANE Select	c.65G>A	p.Arg22Gln	missense	Exon 1 of 5	ENSP00000313362.6	P56270-1
	MAZ	ENST00000219782.11	TSL:1	c.65G>A	p.Arg22Gln	missense	Exon 1 of 6	ENSP00000219782.6	P56270-2
	MAZ	ENST00000545521.5	TSL:1	c.37-41G>A		intron	N/A	ENSP00000443956.1	P56270-3

Frequencies

GnomAD3 genomes AF: 0.0000135 AC: 2 AN: 147772 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000490

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

GnomAD2 exomes AF: 0.00000651 AC: 1 AN: 153634 AF XY: 0.0000113

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: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000391 AC: 5 AN: 1278452 Hom.: 0 Cov.: 32 AF XY: 0.00000472 AC XY: 3 AN XY: 635496

African (AFR) AF: 0.00 AC: 0 AN: 24230

American (AMR) AF: 0.00 AC: 0 AN: 21438

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19830

East Asian (EAS) AF: 0.00 AC: 0 AN: 28050

South Asian (SAS) AF: 0.0000722 AC: 5 AN: 69246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46154

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4994

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1014634

Other (OTH) AF: 0.00 AC: 0 AN: 49876

GnomAD4 genome AF: 0.0000135 AC: 2 AN: 147772 Hom.: 0 Cov.: 30 AF XY: 0.0000139 AC XY: 1 AN XY: 72010

African (AFR) AF: 0.0000490 AC: 2 AN: 40844

American (AMR) AF: 0.00 AC: 0 AN: 14948

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3410

East Asian (EAS) AF: 0.00 AC: 0 AN: 5042

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9048

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66414

Other (OTH) AF: 0.00 AC: 0 AN: 2040

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000838 AC: 1

ClinVar

ClinVar submissions as Germline

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	Benign	0.13
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.74	T
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.028
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.030
Sift	Uncertain	0.014	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.14
MutPred		0.35		Loss of methylation at R22 (P = 0.0281)
MVP		0.20
MPC		0.013
ClinPred		0.036	T
GERP RS		-1.5
PromoterAI		-0.042	Neutral
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		2.2
Varity_R		0.090
gMVP		0.13
Mutation Taster		=95/5	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: rs755933237; hg19: chr16-29818087;