Genetic Variant MZF1:p.Thr405Thr (chr19-58563062-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_198055.2(MZF1):c.1215G>A(p.Thr405Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0682 in 1,602,794 control chromosomes in the GnomAD database, including 9,028 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 3353 hom., cov: 34)

Exomes 𝑓: 0.060 ( 5675 hom. )

Consequence

MZF1
NM_198055.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.88

Variant links:

Genes affected

MZF1 (HGNC:13108): (myeloid zinc finger 1) Enables DNA-binding transcription factor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and protein homodimerization activity. Involved in negative regulation of transcription by RNA polymerase II and positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MZF1 links:

MZF1-AS1 (HGNC:51271): (MZF1 antisense RNA 1)

MZF1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP7

Synonymous conserved (PhyloP=-2.88 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MZF1	NM_198055.2 link	c.1215G>A	p.Thr405Thr	synonymous_variant	Exon 6 of 6	ENST00000215057.7	NP_932172.1	P28698-1A0A024R4T5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MZF1	ENST00000215057.7 link	c.1215G>A	p.Thr405Thr	synonymous_variant	Exon 6 of 6	1	NM_198055.2	ENSP00000215057.1		P28698-1

Frequencies

GnomAD3 genomes

AF:

0.149

AC:

22677

AN:

152122

Hom.:

3345

Cov.:

show subpopulations

Gnomad AFR

AF:

0.378

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.0366

Gnomad EAS

AF:

0.102

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.0391

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0401

Gnomad OTH

AF:

0.120

GnomAD3 exomes

AF:

0.104

AC:

23849

AN:

229974

Hom.:

2320

AF XY:

0.0930

AC XY:

11822

AN XY:

127130

show subpopulations

Gnomad AFR exome

AF:

0.397

Gnomad AMR exome

AF:

0.208

Gnomad ASJ exome

AF:

0.0441

Gnomad EAS exome

AF:

0.0909

Gnomad SAS exome

AF:

0.125

Gnomad FIN exome

AF:

0.0428

Gnomad NFE exome

AF:

0.0396

Gnomad OTH exome

AF:

0.0792

GnomAD4 exome

AF:

0.0597

AC:

86583

AN:

1450554

Hom.:

5675

Cov.:

AF XY:

0.0600

AC XY:

43331

AN XY:

721938

show subpopulations

Gnomad4 AFR exome

AF:

0.396

Gnomad4 AMR exome

AF:

0.204

Gnomad4 ASJ exome

AF:

0.0440

Gnomad4 EAS exome

AF:

0.109

Gnomad4 SAS exome

AF:

0.123

Gnomad4 FIN exome

AF:

0.0446

Gnomad4 NFE exome

AF:

0.0371

Gnomad4 OTH exome

AF:

0.0763

GnomAD4 genome

AF:

0.149

AC:

22715

AN:

152240

Hom.:

3353

Cov.:

AF XY:

0.146

AC XY:

10899

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.378

Gnomad4 AMR

AF:

0.155

Gnomad4 ASJ

AF:

0.0366

Gnomad4 EAS

AF:

0.102

Gnomad4 SAS

AF:

0.119

Gnomad4 FIN

AF:

0.0391

Gnomad4 NFE

AF:

0.0401

Gnomad4 OTH

AF:

0.119

Alfa

AF:

0.0443

Hom.:

111

Bravo

AF:

0.170

Asia WGS

AF:

0.152

AC:

529

AN:

3478

EpiCase

AF:

0.0415

EpiControl

AF:

0.0407

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.3

DANN

Benign

0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over