16-29807023-C-G

Variant names:

• chr16-29807023-C-G
• rs988520613
• NM_002383.4:c.238C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002383.4(MAZ):​c.238C>G​(p.Pro80Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,006,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: MAZ NM_002383.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.882
• Publications: 1 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]

ENSG00000259952 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08503467).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002383.4. 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.238C>G	p.Pro80Ala	missense	Exon 2 of 5	NP_002374.2	P56270-1
	MAZ	NM_001042539.3		c.238C>G	p.Pro80Ala	missense	Exon 2 of 6	NP_001036004.1	P56270-2
	MAZ	NM_001276275.2		c.169C>G	p.Pro57Ala	missense	Exon 3 of 6	NP_001263204.1	P56270-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAZ	ENST00000322945.11	TSL:1 MANE Select	c.238C>G	p.Pro80Ala	missense	Exon 2 of 5	ENSP00000313362.6	P56270-1
	MAZ	ENST00000219782.11	TSL:1	c.238C>G	p.Pro80Ala	missense	Exon 2 of 6	ENSP00000219782.6	P56270-2
	MAZ	ENST00000545521.5	TSL:1	c.169C>G	p.Pro57Ala	missense	Exon 3 of 6	ENSP00000443956.1	P56270-3

Frequencies

GnomAD3 genomes AF: 0.0000273 AC: 4 AN: 146458 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

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: 0.0000607

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000116 AC: 1 AN: 860382 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 401864

African (AFR) AF: 0.00 AC: 0 AN: 16190

American (AMR) AF: 0.00 AC: 0 AN: 1890

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5610

East Asian (EAS) AF: 0.00 AC: 0 AN: 4550

South Asian (SAS) AF: 0.00 AC: 0 AN: 17756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1738

European-Non Finnish (NFE) AF: 0.00000128 AC: 1 AN: 781396

Other (OTH) AF: 0.00 AC: 0 AN: 28728

GnomAD4 genome AF: 0.0000273 AC: 4 AN: 146458 Hom.: 0 Cov.: 31 AF XY: 0.0000281 AC XY: 2 AN XY: 71236

African (AFR) AF: 0.00 AC: 0 AN: 40744

American (AMR) AF: 0.00 AC: 0 AN: 14766

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3390

East Asian (EAS) AF: 0.00 AC: 0 AN: 5030

South Asian (SAS) AF: 0.00 AC: 0 AN: 4804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8638

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.0000607 AC: 4 AN: 65866

Other (OTH) AF: 0.00 AC: 0 AN: 2008

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions as Germline

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	0.092
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.085	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.88
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.029
Sift	Uncertain	0.018	D
Sift4G	Benign	0.62	T
Polyphen		0.0030	B
Vest4		0.23
MutPred		0.26		Loss of loop (P = 0.0203)
MVP		0.26
MPC		0.93
ClinPred		0.11	T
GERP RS		1.3
PromoterAI		0.14	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.3
Varity_R		0.051
gMVP		0.33
Mutation Taster		=78/22	polymorphism

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: rs988520613; hg19: chr16-29818344;