10-43557268-C-T

Variant summary

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

The NM_001099282.2(ZNF239):​c.812G>A​(p.Gly271Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,614,022 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: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

ZNF239
NM_001099282.2 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.19
Variant links:
Genes affected
ZNF239 (HGNC:13031): (zinc finger protein 239) MOK2 proteins are DNA- and RNA-binding proteins that are mainly associated with nuclear RNP components, including the nucleoli and extranucleolar structures (Arranz et al., 1997 [PubMed 9121460]).[supplied by OMIM, Mar 2008]

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=0.2597812).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF239NM_001099282.2 linkc.812G>A p.Gly271Asp missense_variant Exon 4 of 4 ENST00000374446.7 NP_001092752.1 Q16600

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF239ENST00000374446.7 linkc.812G>A p.Gly271Asp missense_variant Exon 4 of 4 1 NM_001099282.2 ENSP00000363569.1 Q16600
ZNF239ENST00000306006.10 linkc.812G>A p.Gly271Asp missense_variant Exon 2 of 2 1 ENSP00000307774.6 Q16600
ZNF239ENST00000426961.1 linkc.812G>A p.Gly271Asp missense_variant Exon 3 of 3 2 ENSP00000398202.1 Q16600
ZNF239ENST00000535642.5 linkc.812G>A p.Gly271Asp missense_variant Exon 2 of 2 2 ENSP00000443907.1 Q16600

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152150
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.000479
GnomAD3 exomes
AF:
0.0000440
AC:
11
AN:
250242
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135710
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000202
Gnomad ASJ exome
AF:
0.0000993
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.0000205
AC:
30
AN:
1461872
Hom.:
0
Cov.:
30
AF XY:
0.0000206
AC XY:
15
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000224
Gnomad4 ASJ exome
AF:
0.0000765
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000135
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152150
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
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:
0.000479
Bravo
AF:
0.0000151
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 08, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.812G>A (p.G271D) alteration is located in exon 2 (coding exon 1) of the ZNF239 gene. This alteration results from a G to A substitution at nucleotide position 812, causing the glycine (G) at amino acid position 271 to be replaced by an aspartic acid (D). 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
0.84
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.44
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.19
T;T;T;T
Eigen
Uncertain
0.25
Eigen_PC
Benign
0.16
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.063
.;.;.;T
M_CAP
Benign
0.0026
T
MetaRNN
Benign
0.26
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.5
L;L;L;L
PrimateAI
Uncertain
0.65
T
PROVEAN
Uncertain
-3.2
D;D;D;D
REVEL
Benign
0.15
Sift
Benign
0.065
T;T;T;T
Sift4G
Benign
0.070
T;T;T;T
Polyphen
1.0
D;D;D;D
Vest4
0.36
MutPred
0.44
Gain of ubiquitination at K267 (P = 0.0445);Gain of ubiquitination at K267 (P = 0.0445);Gain of ubiquitination at K267 (P = 0.0445);Gain of ubiquitination at K267 (P = 0.0445);
MVP
0.16
MPC
0.36
ClinPred
0.45
T
GERP RS
3.8
Varity_R
0.29
gMVP
0.056

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: rs769094106; hg19: chr10-44052716; API