16-29807317-T-G

Position:

• chr16-29807317-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002383.4(MAZ):​c.532T>G​(p.Ser178Ala) 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. 14/21 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. S178C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAZ NM_002383.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.185

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]

(HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0668506).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAZ	NM_002383.4	c.532T>G	p.Ser178Ala	missense_variant	2/5	ENST00000322945.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAZ	ENST00000322945.11	c.532T>G	p.Ser178Ala	missense_variant	2/5	1	NM_002383.4
	ENST00000566537.1	n.416A>C		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2021

The c.532T>G (p.S178A) alteration is located in exon 2 (coding exon 2) of the MAZ gene. This alteration results from a T to G substitution at nucleotide position 532, causing the serine (S) at amino acid position 178 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.58
DEOGEN2	Benign	0.12	.;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.39	T;T;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.067	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	.;N;N
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.18	N;N;N
REVEL	Benign	0.0060
Sift	Benign	0.40	T;T;T
Sift4G	Benign	0.76	T;T;T
Polyphen		0.0010	.;B;.
Vest4		0.22
MutPred		0.38		.;Loss of glycosylation at S178 (P = 0.0233);Loss of glycosylation at S178 (P = 0.0233);
MVP		0.39
MPC		0.81
ClinPred		0.030	T
GERP RS		-0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.044
gMVP		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-29818638;