16-29809692-G-A

Variant names:

• chr16-29809692-G-A
• rs374008621
• ENST00000219782.11:c.1432G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001042539.3(MAZ):​c.1432G>A​(p.Ala478Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000657 in 1,521,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000053 (0 hom.)
• Consequence: MAZ NM_001042539.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.934
• Publications: 0 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]

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

ENSG00000280607 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04106775).
• BS2: High AC in GnomAd4 at 28 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042539.3. 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.1280-385G>A		intron	N/A	NP_002374.2	P56270-1
	MAZ	NM_001042539.3		c.1432G>A	p.Ala478Thr	missense	Exon 5 of 6	NP_001036004.1	P56270-2
	MAZ	NM_001276275.2		c.1211-385G>A		intron	N/A	NP_001263204.1	P56270-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAZ	ENST00000219782.11	TSL:1	c.1432G>A	p.Ala478Thr	missense	Exon 5 of 6	ENSP00000219782.6	P56270-2
	MAZ	ENST00000322945.11	TSL:1 MANE Select	c.1280-385G>A		intron	N/A	ENSP00000313362.6	P56270-1
	MAZ	ENST00000545521.5	TSL:1	c.1211-385G>A		intron	N/A	ENSP00000443956.1	P56270-3

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152182 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000627

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000722 AC: 11 AN: 152366 AF XY: 0.0000234

Gnomad AFR exome AF: 0.000807

Gnomad AMR exome AF: 0.0000468

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000751

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000145

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000526 AC: 72 AN: 1368994 Hom.: 0 Cov.: 32 AF XY: 0.0000460 AC XY: 31 AN XY: 673834

African (AFR) AF: 0.00161 AC: 49 AN: 30508

American (AMR) AF: 0.0000614 AC: 2 AN: 32566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22102

East Asian (EAS) AF: 0.0000267 AC: 1 AN: 37424

South Asian (SAS) AF: 0.00 AC: 0 AN: 76924

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42286

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4638

European-Non Finnish (NFE) AF: 0.0000159 AC: 17 AN: 1066176

Other (OTH) AF: 0.0000532 AC: 3 AN: 56370

GnomAD4 genome AF: 0.000184 AC: 28 AN: 152300 Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17 AN XY: 74478

African (AFR) AF: 0.000626 AC: 26 AN: 41562

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68000

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000130 Hom.: 0

Bravo AF: 0.000302

ESP6500AA AF: 0.000847 AC: 3

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000103 AC: 12

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

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	0.076
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Uncertain	0.98
Eigen	Benign	-0.078
Eigen_PC	Benign	0.021
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.60	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.041	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.93
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.046
Sift	Benign	0.17	T
Sift4G	Benign	0.40	T
Vest4		0.43
MVP		0.32
MPC		0.93
ClinPred		0.049	T
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
gMVP		0.090

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: rs374008621; hg19: chr16-29821013;