rs1401164315

Variant names:

• chr16-29807131-C-T
• rs1401164315
• NM_002383.4:c.346C>T

Variant summary

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

The NM_002383.4(MAZ):​c.346C>T​(p.Pro116Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000224 in 1,025,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000094 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: MAZ NM_002383.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0770
• 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]

ENSG00000259952 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0021101534).
• BS2: High AC in GnomAd4 at 14 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.346C>T	p.Pro116Ser	missense	Exon 2 of 5	NP_002374.2	P56270-1
	MAZ	NM_001042539.3		c.346C>T	p.Pro116Ser	missense	Exon 2 of 6	NP_001036004.1	P56270-2
	MAZ	NM_001276275.2		c.277C>T	p.Pro93Ser	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.346C>T	p.Pro116Ser	missense	Exon 2 of 5	ENSP00000313362.6	P56270-1
	MAZ	ENST00000219782.11	TSL:1	c.346C>T	p.Pro116Ser	missense	Exon 2 of 6	ENSP00000219782.6	P56270-2
	MAZ	ENST00000545521.5	TSL:1	c.277C>T	p.Pro93Ser	missense	Exon 3 of 6	ENSP00000443956.1	P56270-3

Frequencies

GnomAD3 genomes AF: 0.0000946 AC: 14 AN: 148064 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000872

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: 0.0000150

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00610 AC: 2 AN: 328 AF XY: 0.00

Gnomad AMR exome AF: 0.167

Gnomad ASJ exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.125

GnomAD4 exome AF: 0.0000103 AC: 9 AN: 877752 Hom.: 0 Cov.: 13 AF XY: 0.00000954 AC XY: 4 AN XY: 419278

African (AFR) AF: 0.00 AC: 0 AN: 17090

American (AMR) AF: 0.000414 AC: 2 AN: 4826

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8856

East Asian (EAS) AF: 0.00 AC: 0 AN: 14296

South Asian (SAS) AF: 0.0000586 AC: 1 AN: 17052

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13778

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2186

European-Non Finnish (NFE) AF: 0.00000652 AC: 5 AN: 767014

Other (OTH) AF: 0.0000306 AC: 1 AN: 32654

GnomAD4 genome AF: 0.0000945 AC: 14 AN: 148172 Hom.: 0 Cov.: 31 AF XY: 0.0000970 AC XY: 7 AN XY: 72194

African (AFR) AF: 0.00 AC: 0 AN: 41054

American (AMR) AF: 0.000871 AC: 13 AN: 14930

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5078

South Asian (SAS) AF: 0.00 AC: 0 AN: 4790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9104

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.0000150 AC: 1 AN: 66556

Other (OTH) AF: 0.00 AC: 0 AN: 2054

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000106

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	0.11
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	13
DANN	Benign	0.90
DEOGEN2	Benign	0.14	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.077
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.015
Sift	Benign	0.43	T
Sift4G	Benign	0.64	T
Polyphen		0.0010	B
Vest4		0.15
MutPred		0.17		Gain of phosphorylation at P116 (P = 0.0162)
MVP		0.22
MPC		0.97
ClinPred		0.021	T
GERP RS		-0.13
PromoterAI		0.064	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.6
Varity_R		0.037
gMVP		0.50
Mutation Taster		=99/1	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: rs1401164315; hg19: chr16-29818452;