16-29810132-A-G

Variant names:

• chr16-29810132-A-G
• rs370120877
• NM_002383.4:c.1335A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_002383.4(MAZ):​c.1335A>G​(p.Ala445Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000995 in 1,607,766 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00075 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (2 hom.)
• Consequence: MAZ NM_002383.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.12
• Publications: 3 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]

ENSG00000280607 (HGNC:):

MVP-DT (HGNC:56029): (MVP divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0040216744).
• BP6: Variant 16-29810132-A-G is Benign according to our data. Variant chr16-29810132-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2646369.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.12 with no splicing effect.
• BS2: High AC in GnomAd4 at 114 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.1335A>G	p.Ala445Ala	synonymous	Exon 5 of 5	NP_002374.2	P56270-1
	MAZ	NM_001276275.2		c.1266A>G	p.Ala422Ala	synonymous	Exon 6 of 6	NP_001263204.1	P56270-3
	MAZ	NM_001276276.2		c.420A>G	p.Ala140Ala	synonymous	Exon 3 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.1335A>G	p.Ala445Ala	synonymous	Exon 5 of 5	ENSP00000313362.6	P56270-1
	MAZ	ENST00000545521.5	TSL:1	c.1266A>G	p.Ala422Ala	synonymous	Exon 6 of 6	ENSP00000443956.1	P56270-3
	MAZ	ENST00000219782.11	TSL:1	c.*78A>G		3_prime_UTR	Exon 6 of 6	ENSP00000219782.6	P56270-2

Frequencies

GnomAD3 genomes AF: 0.000754 AC: 114 AN: 151270 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000682

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000263

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00273

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000989

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000839 AC: 202 AN: 240634 AF XY: 0.000703

Gnomad AFR exome AF: 0.000856

Gnomad AMR exome AF: 0.000234

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00276

Gnomad FIN exome AF: 0.0000953

Gnomad NFE exome AF: 0.00113

Gnomad OTH exome AF: 0.000513

GnomAD4 exome AF: 0.00102 AC: 1485 AN: 1456376 Hom.: 2 Cov.: 33 AF XY: 0.000944 AC XY: 684 AN XY: 724486

African (AFR) AF: 0.000570 AC: 19 AN: 33348

American (AMR) AF: 0.000247 AC: 11 AN: 44540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26060

East Asian (EAS) AF: 0.00373 AC: 148 AN: 39630

South Asian (SAS) AF: 0.000186 AC: 16 AN: 86120

European-Finnish (FIN) AF: 0.0000958 AC: 5 AN: 52212

Middle Eastern (MID) AF: 0.000531 AC: 3 AN: 5654

European-Non Finnish (NFE) AF: 0.00113 AC: 1251 AN: 1108706

Other (OTH) AF: 0.000532 AC: 32 AN: 60106

GnomAD4 genome AF: 0.000753 AC: 114 AN: 151390 Hom.: 0 Cov.: 32 AF XY: 0.000689 AC XY: 51 AN XY: 74006

African (AFR) AF: 0.000680 AC: 28 AN: 41184

American (AMR) AF: 0.000263 AC: 4 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00274 AC: 14 AN: 5108

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4782

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000989 AC: 67 AN: 67720

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00106 Hom.: 0

ESP6500AA AF: 0.000519 AC: 2

ESP6500EA AF: 0.000880 AC: 7

ExAC AF: 0.000975 AC: 117

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	0.076
DANN	Benign	0.57
FATHMM_MKL	Benign	0.0085	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.0040	T
PhyloP100		-2.1
PROVEAN	Benign	0.71	N
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.22	T
Vest4		0.087
MVP		0.30
GERP RS		-6.5
Mutation Taster		=93/7	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: rs370120877; hg19: chr16-29821453; COSMIC: COSV99360871; COSMIC: COSV99360871;