rs988520613

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-29807023-C-A
• chr16-29807023-C-G
• chr16-29807023-C-T

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>A​(p.Pro80Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000232 in 860,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P80A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: MAZ NM_002383.4 missense
• Clinical Significance: Not reported in ClinVar
• 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=0.08830452).

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>A	p.Pro80Thr	missense	Exon 2 of 5	NP_002374.2	P56270-1
	MAZ	NM_001042539.3		c.238C>A	p.Pro80Thr	missense	Exon 2 of 6	NP_001036004.1	P56270-2
	MAZ	NM_001276275.2		c.169C>A	p.Pro57Thr	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>A	p.Pro80Thr	missense	Exon 2 of 5	ENSP00000313362.6	P56270-1
	MAZ	ENST00000219782.11	TSL:1	c.238C>A	p.Pro80Thr	missense	Exon 2 of 6	ENSP00000219782.6	P56270-2
	MAZ	ENST00000545521.5	TSL:1	c.169C>A	p.Pro57Thr	missense	Exon 3 of 6	ENSP00000443956.1	P56270-3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000232 AC: 2 AN: 860382 Hom.: 0 Cov.: 30 AF XY: 0.00000498 AC XY: 2 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: 0.000575 AC: 1 AN: 1738

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

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

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.88
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.024
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.067	T
Polyphen		0.069	B
Vest4		0.21
MutPred		0.23		Loss of loop (P = 0.0374)
MVP		0.19
MPC		1.1
ClinPred		0.18	T
GERP RS		1.3
PromoterAI		-0.010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.3
Varity_R		0.10
gMVP		0.44
Mutation Taster		=80/20	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;