19-58562680-G-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_198055.2(MZF1):​c.1597C>A​(p.Arg533Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

MZF1
NM_198055.2 missense

Scores

3
4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.287
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-AS1 (HGNC:51271): (MZF1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.30035874).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MZF1NM_198055.2 linkuse as main transcriptc.1597C>A p.Arg533Ser missense_variant 6/6 ENST00000215057.7 NP_932172.1 P28698-1A0A024R4T5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MZF1ENST00000215057.7 linkuse as main transcriptc.1597C>A p.Arg533Ser missense_variant 6/61 NM_198055.2 ENSP00000215057.1 P28698-1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
148424
Hom.:
0
Cov.:
34
FAILED QC
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1387412
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
685122
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
148544
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
72480
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
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:
0.00

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 submitterclinical testingAmbry GeneticsAug 20, 2024The c.1597C>A (p.R533S) alteration is located in exon 6 (coding exon 5) of the MZF1 gene. This alteration results from a C to A substitution at nucleotide position 1597, causing the arginine (R) at amino acid position 533 to be replaced by a serine (S). 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
0.91
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.45
T;T
Eigen
Benign
-0.38
Eigen_PC
Benign
-0.48
FATHMM_MKL
Benign
0.053
N
LIST_S2
Benign
0.24
.;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.30
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L;L
PrimateAI
Pathogenic
0.89
D
PROVEAN
Pathogenic
-4.6
D;.
REVEL
Benign
0.12
Sift
Uncertain
0.0050
D;.
Sift4G
Uncertain
0.0040
D;D
Polyphen
0.61
P;P
Vest4
0.25
MutPred
0.76
Loss of MoRF binding (P = 0.0513);Loss of MoRF binding (P = 0.0513);
MVP
0.50
MPC
1.9
ClinPred
0.84
D
GERP RS
1.4
Varity_R
0.34
gMVP
0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-59074047; API