Variant 19-58562766-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_198055.2(MZF1):c.1511A>T(p.Gln504Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00301 in 1,535,388 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0020 ( 2 hom., cov: 34)

Exomes 𝑓: 0.0031 ( 8 hom. )

Consequence

MZF1
NM_198055.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.440

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.039498568).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MZF1	NM_198055.2 link	c.1511A>T	p.Gln504Leu	missense_variant	6/6	ENST00000215057.7	NP_932172.1	P28698-1A0A024R4T5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MZF1	ENST00000215057.7 link	c.1511A>T	p.Gln504Leu	missense_variant	6/6	1	NM_198055.2	ENSP00000215057.1		P28698-1

Frequencies

GnomAD3 genomes

AF:

0.00205

AC:

311

AN:

151958

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00329

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.00145

AC:

190

AN:

131144

Hom.:

AF XY:

0.00142

AC XY:

102

AN XY:

71842

show subpopulations

Gnomad AFR exome

AF:

0.000790

Gnomad AMR exome

AF:

0.000572

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00288

Gnomad NFE exome

AF:

0.00308

Gnomad OTH exome

AF:

0.000741

GnomAD4 exome

AF:

0.00312

AC:

4316

AN:

1383310

Hom.:

Cov.:

AF XY:

0.00303

AC XY:

2069

AN XY:

682738

show subpopulations

Gnomad4 AFR exome

AF:

0.000539

Gnomad4 AMR exome

AF:

0.000616

Gnomad4 ASJ exome

AF:

0.0000398

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00193

Gnomad4 NFE exome

AF:

0.00379

Gnomad4 OTH exome

AF:

0.00204

GnomAD4 genome

AF:

0.00204

AC:

311

AN:

152078

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

127

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00245

Gnomad4 NFE

AF:

0.00330

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.00158

Hom.:

Bravo

AF:

0.00189

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.00116

AC:

ESP6500EA

AF:

0.00240

AC:

ExAC

AF:

0.000604

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2021

The c.1511A>T (p.Q504L) alteration is located in exon 6 (coding exon 5) of the MZF1 gene. This alteration results from a A to T substitution at nucleotide position 1511, causing the glutamine (Q) at amino acid position 504 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.41

T;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.51

.;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.039

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.57

N;N

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-5.2

D;.

REVEL

Benign

0.18

Sift

Benign

0.10

T;.

Sift4G

Benign

0.072

T;T

Polyphen

0.62

P;P

Vest4

0.55

MVP

0.53

MPC

1.7

ClinPred

0.037

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.33

gMVP

0.38

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over