Genetic Variant NM_198055.2:c.991A>C (chr19-58563286-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198055.2(MZF1):c.991A>C(p.Ile331Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

MZF1
NM_198055.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.512

Publications

27 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05049628).

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.991A>C	p.Ile331Leu	missense	Exon 6 of 6	NP_932172.1	P28698-1
MZF1	NM_003422.3		c.991A>C	p.Ile331Leu	missense	Exon 6 of 6	NP_003413.2
MZF1	NM_001267033.2		c.773-26A>C		intron	N/A	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.991A>C	p.Ile331Leu	missense	Exon 6 of 6	ENSP00000215057.1	P28698-1
MZF1	ENST00000599369.5	TSL:1	c.991A>C	p.Ile331Leu	missense	Exon 6 of 6	ENSP00000469493.1	P28698-1
MZF1	ENST00000594234.5	TSL:1	c.773-26A>C		intron	N/A	ENSP00000469378.1	P28698-3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152006

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41394

American (AMR)

AF:

0.00

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10586

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67958

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

6677

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.6

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.077

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.22

M_CAP

Benign

0.0016

MetaRNN

Benign

0.050

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

PhyloP100

0.51

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.090

REVEL

Benign

0.022

Sift

Benign

0.69

Sift4G

Benign

0.40

Polyphen

0.0

Vest4

0.10

MutPred

0.15

Loss of MoRF binding (P = 0.1236)

MVP

0.25

MPC

0.057

ClinPred

0.031

GERP RS

2.5

La Branchor

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.041

gMVP

0.059

Mutation Taster

=100/0

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

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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