chr16-29806735-C-A

Variant names:

• chr16-29806735-C-A
• rs530190319
• NM_002383.4:c.34C>A

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.34C>A​(p.Pro12Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,242,904 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P12S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: MAZ NM_002383.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.329
• Publications: 2 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=0.08188975).
• BS2: High AC in GnomAdExome4 at 40 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.34C>A	p.Pro12Thr	missense	Exon 1 of 5	NP_002374.2	P56270-1
	MAZ	NM_001042539.3		c.34C>A	p.Pro12Thr	missense	Exon 1 of 6	NP_001036004.1	P56270-2
	MAZ	NM_001276276.2		c.34C>A	p.Pro12Thr	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.34C>A	p.Pro12Thr	missense	Exon 1 of 5	ENSP00000313362.6	P56270-1
	MAZ	ENST00000219782.11	TSL:1	c.34C>A	p.Pro12Thr	missense	Exon 1 of 6	ENSP00000219782.6	P56270-2
	MAZ	ENST00000545521.5	TSL:1	c.37-72C>A		intron	N/A	ENSP00000443956.1	P56270-3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.00000632 AC: 1 AN: 158228 AF XY: 0.0000110

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: 0.0000322 AC: 40 AN: 1242904 Hom.: 0 Cov.: 32 AF XY: 0.0000405 AC XY: 25 AN XY: 617456

African (AFR) AF: 0.00 AC: 0 AN: 23890

American (AMR) AF: 0.00 AC: 0 AN: 23594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18802

East Asian (EAS) AF: 0.00 AC: 0 AN: 27040

South Asian (SAS) AF: 0.0000152 AC: 1 AN: 65748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43566

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4764

European-Non Finnish (NFE) AF: 0.0000395 AC: 39 AN: 988286

Other (OTH) AF: 0.00 AC: 0 AN: 47214

GnomAD4 genome Cov.: 30

Alfa AF: 0.0000285 Hom.: 0

ExAC AF: 0.0000168 AC: 2

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	0.17
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.082	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.33
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.034
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0	B
Vest4		0.18
MVP		0.13
MPC		0.013
ClinPred		0.16	T
GERP RS		-0.20
PromoterAI		-0.077	Neutral
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.3
Varity_R		0.14
gMVP		0.16
Mutation Taster		=99/1	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: rs530190319; hg19: chr16-29818056;