Genetic Variant NM_198055.2:c.2051C>A (chr19-58562226-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198055.2(MZF1):c.2051C>A(p.Pro684His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MZF1
NM_198055.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.832

Publications

0 publications found

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 was made for transcript

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=0.12833673).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198055.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MZF1	NM_198055.2	MANE Select	c.2051C>A	p.Pro684His	missense	Exon 6 of 6	NP_932172.1	P28698-1
MZF1	NM_003422.3		c.2051C>A	p.Pro684His	missense	Exon 6 of 6	NP_003413.2
MZF1	NM_001267033.2		c.*934C>A		3_prime_UTR	Exon 6 of 6	NP_001253962.1	P28698-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MZF1	ENST00000215057.7	TSL:1 MANE Select	c.2051C>A	p.Pro684His	missense	Exon 6 of 6	ENSP00000215057.1	P28698-1
MZF1	ENST00000599369.5	TSL:1	c.2051C>A	p.Pro684His	missense	Exon 6 of 6	ENSP00000469493.1	P28698-1
MZF1	ENST00000594234.5	TSL:1	c.*934C>A		3_prime_UTR	Exon 6 of 6	ENSP00000469378.1	P28698-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1456876

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724946

African (AFR)

AF:

0.00

AC:

AN:

33328

American (AMR)

AF:

0.00

AC:

AN:

44452

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26038

East Asian (EAS)

AF:

0.00

AC:

AN:

39638

South Asian (SAS)

AF:

0.00

AC:

AN:

86072

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50060

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111236

Other (OTH)

AF:

0.00

AC:

AN:

60290

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.076

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.089

M_CAP

Benign

0.0086

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PhyloP100

-0.83

PrimateAI

Uncertain

0.75

PROVEAN

Benign

0.22

REVEL

Benign

0.044

Sift

Benign

0.23

Sift4G

Benign

0.20

Polyphen

0.10

Vest4

0.37

MutPred

0.24

Gain of MoRF binding (P = 0.0668)

MVP

0.52

MPC

1.8

ClinPred

0.50

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.16

gMVP

0.31

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over