16-29807099-C-T

Position:

• chr16-29807099-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_002383.4(MAZ):​c.314C>T​(p.Ala105Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000815 in 859,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000081 (0 hom.)
• Consequence: MAZ NM_002383.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.274

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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10602069).
• BS2: High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MAZ	NM_002383.4	c.314C>T	p.Ala105Val	missense_variant	2/5	ENST00000322945.11	NP_002374.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MAZ	ENST00000322945.11	c.314C>T	p.Ala105Val	missense_variant	2/5	1	NM_002383.4	ENSP00000313362.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000815 AC: 7 AN: 859054 Hom.: 0 Cov.: 14 AF XY: 0.0000123 AC XY: 5 AN XY: 408124

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000907

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.0000151

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 05, 2024

The c.314C>T (p.A105V) alteration is located in exon 2 (coding exon 2) of the MAZ gene. This alteration results from a C to T substitution at nucleotide position 314, causing the alanine (A) at amino acid position 105 to be replaced by a valine (V). 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	0.19
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	.;T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.65	T;T;T
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	.;N;N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.52	N;N;N
REVEL	Benign	0.025
Sift	Benign	0.056	T;D;D
Sift4G	Benign	0.14	T;T;T
Polyphen		0.0010	.;B;.
Vest4		0.28
MutPred		0.43		.;Gain of catalytic residue at A105 (P = 0.0203);Gain of catalytic residue at A105 (P = 0.0203);
MVP		0.48
MPC		1.7
ClinPred		0.098	T
GERP RS		2.1
Varity_R		0.084
gMVP		0.44

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: rs1423036978; hg19: chr16-29818420;