rs149765326

Variant summary

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

The NM_014650.4(ZNF432):​c.1495G>C​(p.Gly499Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

ZNF432
NM_014650.4 missense

Scores

1
2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.69
Variant links:
Genes affected
ZNF432 (HGNC:20810): (zinc finger protein 432) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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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=0.2247149).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF432NM_014650.4 linkc.1495G>C p.Gly499Arg missense_variant Exon 5 of 5 ENST00000221315.10 NP_055465.1 O94892A0A024R4I3
ZNF432NM_001322284.2 linkc.1495G>C p.Gly499Arg missense_variant Exon 5 of 5 NP_001309213.1 O94892A0A024R4I3
ZNF432NM_001322285.1 linkc.1495G>C p.Gly499Arg missense_variant Exon 5 of 5 NP_001309214.1 O94892A0A024R4I3
ZNF432XM_024451806.2 linkc.1207G>C p.Gly403Arg missense_variant Exon 2 of 2 XP_024307574.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF432ENST00000221315.10 linkc.1495G>C p.Gly499Arg missense_variant Exon 5 of 5 1 NM_014650.4 ENSP00000221315.4 O94892
ZNF432ENST00000594154.5 linkc.1495G>C p.Gly499Arg missense_variant Exon 5 of 5 1 ENSP00000470488.1 O94892

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461818
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727206
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:
0.00000180
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.91
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
14
DANN
Uncertain
0.99
DEOGEN2
Benign
0.022
T;T
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.33
FATHMM_MKL
Benign
0.00033
N
LIST_S2
Benign
0.61
.;T
M_CAP
Benign
0.0016
T
MetaRNN
Benign
0.22
T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.14
N;N
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
-1.2
.;N
REVEL
Benign
0.13
Sift
Benign
0.27
.;T
Sift4G
Benign
0.64
T;T
Polyphen
0.98
D;D
Vest4
0.34
MutPred
0.31
Gain of MoRF binding (P = 0.0272);Gain of MoRF binding (P = 0.0272);
MVP
0.29
MPC
0.29
ClinPred
0.37
T
GERP RS
1.6
Varity_R
0.070
gMVP
0.067

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: chr19-52537437; API