chr19-12349883-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_030824.3(ZNF442):​c.1702G>A​(p.Gly568Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000706 in 1,613,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000067 ( 0 hom. )

Consequence

ZNF442
NM_030824.3 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.696
Variant links:
Genes affected
ZNF442 (HGNC:20877): (zinc finger protein 442) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07019618).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF442NM_030824.3 linkc.1702G>A p.Gly568Arg missense_variant Exon 6 of 6 ENST00000242804.9 NP_110451.1 Q9H7R0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF442ENST00000242804.9 linkc.1702G>A p.Gly568Arg missense_variant Exon 6 of 6 2 NM_030824.3 ENSP00000242804.4 Q9H7R0-1
ZNF442ENST00000545749.2 linkc.1702G>A p.Gly568Arg missense_variant Exon 4 of 4 5 ENSP00000440162.2 Q9H7R0-1
ZNF442ENST00000438182.5 linkc.1495G>A p.Gly499Arg missense_variant Exon 3 of 3 2 ENSP00000388634.1 Q9H7R0-2

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
151692
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000657
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:
0.000206
Gnomad OTH
AF:
0.000480
GnomAD3 exomes
AF:
0.0000994
AC:
25
AN:
251438
Hom.:
0
AF XY:
0.0000883
AC XY:
12
AN XY:
135892
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.000202
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000670
AC:
98
AN:
1461848
Hom.:
0
Cov.:
31
AF XY:
0.0000729
AC XY:
53
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000447
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:
0.0000755
Gnomad4 OTH exome
AF:
0.000166
GnomAD4 genome
AF:
0.000105
AC:
16
AN:
151810
Hom.:
0
Cov.:
32
AF XY:
0.0000809
AC XY:
6
AN XY:
74192
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.0000656
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.000475
Alfa
AF:
0.0000984
Hom.:
0
Bravo
AF:
0.000110
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.000123
AC:
15
EpiCase
AF:
0.000164
EpiControl
AF:
0.000296

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 07, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1702G>A (p.G568R) alteration is located in exon 6 (coding exon 4) of the ZNF442 gene. This alteration results from a G to A substitution at nucleotide position 1702, causing the glycine (G) at amino acid position 568 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
0.24
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
12
DANN
Uncertain
0.99
DEOGEN2
Benign
0.035
T;.;T
Eigen
Benign
-0.49
Eigen_PC
Benign
-0.74
FATHMM_MKL
Benign
0.00056
N
LIST_S2
Benign
0.23
.;T;T
M_CAP
Benign
0.0016
T
MetaRNN
Benign
0.070
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L;.;L
PrimateAI
Benign
0.29
T
PROVEAN
Pathogenic
-4.5
D;D;.
REVEL
Benign
0.042
Sift
Benign
0.069
T;T;.
Sift4G
Uncertain
0.034
D;D;D
Polyphen
0.72
P;.;P
Vest4
0.10
MutPred
0.60
Gain of MoRF binding (P = 0.0081);.;Gain of MoRF binding (P = 0.0081);
MVP
0.32
MPC
0.091
ClinPred
0.20
T
GERP RS
0.79
Varity_R
0.11
gMVP
0.013

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.

Other links and lift over

dbSNP: rs150152603; hg19: chr19-12460697; API