chr19-58562737-C-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_198055.2(MZF1):​c.1540G>C​(p.Gly514Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000348 in 1,536,222 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.00017 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00037 ( 0 hom. )

Consequence

MZF1
NM_198055.2 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -5.40

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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.032491565).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MZF1NM_198055.2 linkc.1540G>C p.Gly514Arg 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
MZF1ENST00000215057.7 linkc.1540G>C p.Gly514Arg missense_variant Exon 6 of 6 1 NM_198055.2 ENSP00000215057.1 P28698-1

Frequencies

GnomAD3 genomes
AF:
0.000171
AC:
26
AN:
152124
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000235
Gnomad OTH
AF:
0.000478
GnomAD2 exomes
AF:
0.000280
AC:
37
AN:
131994
AF XY:
0.000290
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000816
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000381
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000367
AC:
508
AN:
1383980
Hom.:
0
Cov.:
31
AF XY:
0.000369
AC XY:
252
AN XY:
683206
show subpopulations
African (AFR)
AF:
0.0000316
AC:
1
AN:
31614
American (AMR)
AF:
0.000112
AC:
4
AN:
35736
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25146
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35804
South Asian (SAS)
AF:
0.000666
AC:
53
AN:
79530
European-Finnish (FIN)
AF:
0.0000593
AC:
2
AN:
33744
Middle Eastern (MID)
AF:
0.000578
AC:
3
AN:
5186
European-Non Finnish (NFE)
AF:
0.000398
AC:
430
AN:
1079366
Other (OTH)
AF:
0.000259
AC:
15
AN:
57854
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.486
Heterozygous variant carriers
0
37
74
112
149
186
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
20
40
60
80
100
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000171
AC:
26
AN:
152242
Hom.:
0
Cov.:
34
AF XY:
0.000161
AC XY:
12
AN XY:
74438
show subpopulations
African (AFR)
AF:
0.000144
AC:
6
AN:
41534
American (AMR)
AF:
0.00
AC:
0
AN:
15304
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5180
South Asian (SAS)
AF:
0.000622
AC:
3
AN:
4826
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10612
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
292
European-Non Finnish (NFE)
AF:
0.000235
AC:
16
AN:
68004
Other (OTH)
AF:
0.000473
AC:
1
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.488
Heterozygous variant carriers
0
1
3
4
6
7
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.000342
Hom.:
0
Bravo
AF:
0.000212
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000519
AC:
2
ExAC
AF:
0.000102
AC:
10
Asia WGS
AF:
0.000289
AC:
1
AN:
3476

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 24, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.1540G>C (p.G514R) alteration is located in exon 6 (coding exon 5) of the MZF1 gene. This alteration results from a G to C substitution at nucleotide position 1540, causing the glycine (G) at amino acid position 514 to be replaced by an arginine (R). 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
Benign
0.23
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
11
DANN
Uncertain
0.99
DEOGEN2
Benign
0.063
T;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.13
N
LIST_S2
Benign
0.20
.;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.032
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.30
N;N
PhyloP100
-5.4
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
1.2
N;.
REVEL
Benign
0.054
Sift
Benign
0.84
T;.
Sift4G
Benign
0.61
T;T
Polyphen
0.12
B;B
Vest4
0.15
MVP
0.20
MPC
1.6
ClinPred
0.055
T
GERP RS
1.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.031
gMVP
0.12
Mutation Taster
=98/2
polymorphism

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

Other links and lift over

dbSNP: rs150590904; hg19: chr19-59074104; API