chr16-29806711-G-C

Variant names:

• chr16-29806711-G-C
• rs757901583
• NM_002383.4:c.10G>C

Variant summary

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

The NM_002383.4(MAZ):​c.10G>C​(p.Val4Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000439 in 1,320,514 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.000061 (1 hom., cov: 30)
  • Exomes 𝑓: 0.000042 (0 hom.)
• Consequence: MAZ NM_002383.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.272
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03986177).
• BS2: High AC in GnomAd4 at 9 AD gene.

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.10G>C	p.Val4Leu	missense	Exon 1 of 5	NP_002374.2	P56270-1
	MAZ	NM_001042539.3		c.10G>C	p.Val4Leu	missense	Exon 1 of 6	NP_001036004.1	P56270-2
	MAZ	NM_001276276.2		c.10G>C	p.Val4Leu	missense	Exon 1 of 3	NP_001263205.1	P56270-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAZ	ENST00000322945.11	TSL:1 MANE Select	c.10G>C	p.Val4Leu	missense	Exon 1 of 5	ENSP00000313362.6	P56270-1
	MAZ	ENST00000219782.11	TSL:1	c.10G>C	p.Val4Leu	missense	Exon 1 of 6	ENSP00000219782.6	P56270-2
	MAZ	ENST00000545521.5	TSL:1	c.37-96G>C		intron	N/A	ENSP00000443956.1	P56270-3

Frequencies

GnomAD3 genomes AF: 0.0000614 AC: 9 AN: 146578 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000269

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00333

Gnomad NFE AF: 0.0000303

Gnomad OTH AF: 0.000986

GnomAD2 exomes AF: 0.0000763 AC: 11 AN: 144132 AF XY: 0.0000719

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000527

Gnomad ASJ exome AF: 0.000167

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000293

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000417 AC: 49 AN: 1173848 Hom.: 0 Cov.: 32 AF XY: 0.0000448 AC XY: 26 AN XY: 580372

African (AFR) AF: 0.00 AC: 0 AN: 22410

American (AMR) AF: 0.000339 AC: 7 AN: 20666

Ashkenazi Jewish (ASJ) AF: 0.0000621 AC: 1 AN: 16116

East Asian (EAS) AF: 0.00 AC: 0 AN: 24362

South Asian (SAS) AF: 0.00 AC: 0 AN: 56508

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37402

Middle Eastern (MID) AF: 0.000713 AC: 3 AN: 4208

European-Non Finnish (NFE) AF: 0.0000327 AC: 31 AN: 948910

Other (OTH) AF: 0.000162 AC: 7 AN: 43266

GnomAD4 genome AF: 0.0000614 AC: 9 AN: 146666 Hom.: 1 Cov.: 30 AF XY: 0.0000560 AC XY: 4 AN XY: 71478

African (AFR) AF: 0.00 AC: 0 AN: 40654

American (AMR) AF: 0.000269 AC: 4 AN: 14886

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3408

East Asian (EAS) AF: 0.00 AC: 0 AN: 4876

South Asian (SAS) AF: 0.00 AC: 0 AN: 4784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8784

Middle Eastern (MID) AF: 0.00357 AC: 1 AN: 280

European-Non Finnish (NFE) AF: 0.0000303 AC: 2 AN: 66046

Other (OTH) AF: 0.000977 AC: 2 AN: 2048

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000831

ExAC AF: 0.0000674 AC: 8

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	0.20
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Benign	0.88
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.73	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.27
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.038
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0010	B
Vest4		0.25
MutPred		0.26		Gain of disorder (P = 0.0963)
MVP		0.10
MPC		0.013
ClinPred		0.10	T
GERP RS		1.1
PromoterAI		-0.0022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.18
gMVP		0.075
Mutation Taster		=98/2	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: rs757901583; hg19: chr16-29818032;