Variant 19-58562345-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000215057.7(MZF1):c.1932G>T(p.Gln644His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,406 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: not found (cov: 34)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MZF1
ENST00000215057.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.257

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33274752).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MZF1	NM_198055.2 linkuse as main transcript	c.1932G>T	p.Gln644His	missense_variant	6/6	ENST00000215057.7	NP_932172.1
MZF1-AS1	NR_027334.2 linkuse as main transcript	n.224+2936C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MZF1	ENST00000215057.7 linkuse as main transcript	c.1932G>T	p.Gln644His	missense_variant	6/6	1	NM_198055.2	ENSP00000215057	P1	P28698-1
MZF1-AS1	ENST00000600534.1 linkuse as main transcript	n.185+2936C>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000409

AC:

AN:

244396

Hom.:

AF XY:

0.00000753

AC XY:

AN XY:

132880

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000911

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1458406

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725488

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 26, 2022

The c.1932G>T (p.Q644H) alteration is located in exon 6 (coding exon 5) of the MZF1 gene. This alteration results from a G to T substitution at nucleotide position 1932, causing the glutamine (Q) at amino acid position 644 to be replaced by a histidine (H). 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

0.74

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

T;T

Eigen

Benign

0.15

Eigen_PC

Benign

0.036

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.36

.;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.33

T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.8

L;L

MutationTaster

Benign

0.87

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.3

D;.

REVEL

Benign

0.049

Sift

Uncertain

0.0020

D;.

Sift4G

Benign

0.068

T;T

Polyphen

1.0

D;D

Vest4

0.22

MutPred

0.41

Gain of phosphorylation at T641 (P = 0.152);Gain of phosphorylation at T641 (P = 0.152);

MVP

0.52

MPC

1.6

ClinPred

0.94

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.49

gMVP

0.31

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