16-29809603-G-A

Position:

• chr16-29809603-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000219782.11(MAZ):​c.1343G>A​(p.Arg448Gln) 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. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MAZ ENST00000219782.11 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.23

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]

LOC112268170 (HGNC:):

MVP-DT (HGNC:56029): (MVP divergent transcript)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3090954).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MAZ	NM_002383.4	c.1280-474G>A		intron_variant		ENST00000322945.11
LOC112268170	XM_047435008.1	c.*1470+432C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MAZ	ENST00000322945.11	c.1280-474G>A		intron_variant		1	NM_002383.4
MVP-DT	ENST00000569039.5	n.384+432C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Jan 23, 2024

The c.1343G>A (p.R448Q) alteration is located in exon 5 (coding exon 5) of the MAZ gene. This alteration results from a G to A substitution at nucleotide position 1343, causing the arginine (R) at amino acid position 448 to be replaced by a glutamine (Q). 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
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.054	.;T;.
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.077
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.81	T;T;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.31	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.58	D;D;D;D;D;D;D;N
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	0.0	N;.;.
REVEL	Benign	0.077
Sift	Benign	0.38	T;.;.
Sift4G	Benign	0.24	T;T;T
Vest4		0.43
MutPred		0.61		Loss of MoRF binding (P = 0.0743);.;.;
MVP		0.50
MPC		2.0
ClinPred		0.97	D
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.11

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: chr16-29820924; COSMIC: COSV105006021; COSMIC: COSV105006021;