chr16-29809563-C-T

Variant names:

• chr16-29809563-C-T
• rs1899786755
• ENST00000219782.11:c.1303C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001042539.3(MAZ):​c.1303C>T​(p.Arg435Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MAZ NM_001042539.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.16
• 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36834812).

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.1280-514C>T		intron	N/A	NP_002374.2	P56270-1
	MAZ	NM_001042539.3		c.1303C>T	p.Arg435Cys	missense	Exon 5 of 6	NP_001036004.1	P56270-2
	MAZ	NM_001276275.2		c.1211-514C>T		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.1303C>T	p.Arg435Cys	missense	Exon 5 of 6	ENSP00000219782.6	P56270-2
	MAZ	ENST00000322945.11	TSL:1 MANE Select	c.1280-514C>T		intron	N/A	ENSP00000313362.6	P56270-1
	MAZ	ENST00000545521.5	TSL:1	c.1211-514C>T		intron	N/A	ENSP00000443956.1	P56270-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459534 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726154

African (AFR) AF: 0.00 AC: 0 AN: 33372

American (AMR) AF: 0.00 AC: 0 AN: 44352

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26034

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111304

Other (OTH) AF: 0.00 AC: 0 AN: 60302

GnomAD4 genome Cov.: 32

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	Pathogenic	0.95
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.2	T
PhyloP100		1.2
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.18
Sift	Benign	0.041	D
Sift4G	Uncertain	0.0020	D
Vest4		0.75
MutPred		0.47		Gain of methylation at K440 (P = 0.0801)
MVP		0.39
MPC		1.3
ClinPred		0.98	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.45
Mutation Taster		=42/58	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1899786755; hg19: chr16-29820884;