Genetic Variant MZF1:p.Gln636Leu (chr19-58562370-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198055.2(MZF1):c.1907A>T(p.Gln636Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,608,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

MZF1
NM_198055.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.367

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18173501).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MZF1	NM_198055.2 link	c.1907A>T	p.Gln636Leu	missense_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.1907A>T	p.Gln636Leu	missense_variant	Exon 6 of 6	1	NM_198055.2	ENSP00000215057.1		P28698-1

Frequencies

GnomAD3 genomes

AF:

0.0000266

AC:

AN:

150370

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000199

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:

0.00

Gnomad OTH

AF:

0.000485

GnomAD3 exomes

AF:

0.000111

AC:

AN:

242380

Hom.:

AF XY:

0.000122

AC XY:

AN XY:

131646

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000746

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000336

GnomAD4 exome

AF:

0.0000199

AC:

AN:

1457770

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

725084

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000614

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000266

AC:

AN:

150370

Hom.:

Cov.:

AF XY:

0.0000409

AC XY:

AN XY:

73410

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000199

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000485

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.000107

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 21, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1907A>T (p.Q636L) 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 1907, causing the glutamine (Q) at amino acid position 636 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

Pathogenic

0.78

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

T;T

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.72

.;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.84

L;L

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-3.5

D;.

REVEL

Benign

0.14

Sift

Uncertain

0.025

D;.

Sift4G

Uncertain

0.027

D;D

Polyphen

1.0

D;D

Vest4

0.42

MutPred

0.49

Gain of stability (P = 0.028);Gain of stability (P = 0.028);

MVP

0.62

MPC

1.7

ClinPred

0.28

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.26

gMVP

0.30

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