NM_002383.4:c.302C>T

Variant names:

• chr16-29807087-C-T
• rs1158236117
• NM_002383.4:c.302C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_002383.4(MAZ):​c.302C>T​(p.Ala101Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000902 in 997,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000071 (0 hom.)
• Consequence: MAZ NM_002383.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0340
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07728225).
• BS2: High AC in GnomAdExome4 at 6 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.302C>T	p.Ala101Val	missense	Exon 2 of 5	NP_002374.2	P56270-1
	MAZ	NM_001042539.3		c.302C>T	p.Ala101Val	missense	Exon 2 of 6	NP_001036004.1	P56270-2
	MAZ	NM_001276275.2		c.233C>T	p.Ala78Val	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.302C>T	p.Ala101Val	missense	Exon 2 of 5	ENSP00000313362.6	P56270-1
	MAZ	ENST00000219782.11	TSL:1	c.302C>T	p.Ala101Val	missense	Exon 2 of 6	ENSP00000219782.6	P56270-2
	MAZ	ENST00000545521.5	TSL:1	c.233C>T	p.Ala78Val	missense	Exon 3 of 6	ENSP00000443956.1	P56270-3

Frequencies

GnomAD3 genomes AF: 0.0000204 AC: 3 AN: 146972 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000393

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000151

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000705 AC: 6 AN: 850550 Hom.: 0 Cov.: 15 AF XY: 0.00000248 AC XY: 1 AN XY: 402954

African (AFR) AF: 0.00 AC: 0 AN: 15932

American (AMR) AF: 0.00 AC: 0 AN: 2504

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5954

East Asian (EAS) AF: 0.00 AC: 0 AN: 5294

South Asian (SAS) AF: 0.00 AC: 0 AN: 18362

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1778

European-Non Finnish (NFE) AF: 0.00000782 AC: 6 AN: 767706

Other (OTH) AF: 0.00 AC: 0 AN: 28888

GnomAD4 genome AF: 0.0000204 AC: 3 AN: 146972 Hom.: 0 Cov.: 31 AF XY: 0.0000420 AC XY: 3 AN XY: 71510

African (AFR) AF: 0.00 AC: 0 AN: 40866

American (AMR) AF: 0.00 AC: 0 AN: 14770

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3396

East Asian (EAS) AF: 0.000393 AC: 2 AN: 5090

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8766

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000151 AC: 1 AN: 66024

Other (OTH) AF: 0.00 AC: 0 AN: 2020

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

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	Benign	0.19
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.034
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	0.12	N
REVEL	Benign	0.081
Sift	Benign	0.85	T
Sift4G	Benign	0.41	T
Polyphen		0.0010	B
Vest4		0.30
MutPred		0.47		Gain of catalytic residue at A101 (P = 0.0185)
MVP		0.51
MPC		0.95
ClinPred		0.10	T
GERP RS		1.0
PromoterAI		0.013	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.040
gMVP		0.42
Mutation Taster		=98/2	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: rs1158236117; hg19: chr16-29818408;