16-29807227-G-A

Variant names:

• chr16-29807227-G-A
• rs1369324219
• NM_002383.4:c.442G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_002383.4(MAZ):​c.442G>A​(p.Ala148Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000431 in 1,160,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: MAZ NM_002383.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.368

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13238496).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAZ	NM_002383.4	c.442G>A	p.Ala148Thr	missense_variant	Exon 2 of 5	ENST00000322945.11	NP_002374.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAZ	ENST00000322945.11	c.442G>A	p.Ala148Thr	missense_variant	Exon 2 of 5	1	NM_002383.4	ENSP00000313362.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000431 AC: 5 AN: 1160690 Hom.: 0 Cov.: 25 AF XY: 0.00000355 AC XY: 2 AN XY: 563028

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000374

Gnomad4 SAS exome AF: 0.0000544

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000208

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.442G>A (p.A148T) alteration is located in exon 2 (coding exon 2) of the MAZ gene. This alteration results from a G to A substitution at nucleotide position 442, causing the alanine (A) at amino acid position 148 to be replaced by a threonine (T). 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	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	.;T;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.72	T;T;T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.0	.;N;N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.27	N;N;N
REVEL	Benign	0.055
Sift	Benign	0.13	T;T;T
Sift4G	Benign	0.53	T;T;T
Polyphen		0.96	.;D;.
Vest4		0.13
MutPred		0.31		.;Gain of glycosylation at A148 (P = 9e-04);Gain of glycosylation at A148 (P = 9e-04);
MVP		0.27
MPC		1.0
ClinPred		0.19	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.081
gMVP		0.31

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

LitVar

Other links and lift over

dbSNP: rs1369324219; hg19: chr16-29818548;