19-21530643-C-G

Variant summary

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

The NM_001001415.4(ZNF429):​c.185C>G​(p.Pro62Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,459,668 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P62H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

ZNF429
NM_001001415.4 missense

Scores

2
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.395
Variant links:
Genes affected
ZNF429 (HGNC:20817): (zinc finger protein 429) 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. Predicted to be active in nucleus. [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=0.15309116).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZNF429NM_001001415.4 linkc.185C>G p.Pro62Arg missense_variant Exon 3 of 4 ENST00000358491.9 NP_001001415.2 Q86V71

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ZNF429ENST00000358491.9 linkc.185C>G p.Pro62Arg missense_variant Exon 3 of 4 3 NM_001001415.4 ENSP00000351280.3 Q86V71
ZNF429ENST00000597078.5 linkc.185C>G p.Pro62Arg missense_variant Exon 3 of 6 1 ENSP00000470300.1 M0QZ47
ZNF429ENST00000594022.1 linkn.570C>G non_coding_transcript_exon_variant Exon 5 of 6 3

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.0000400
AC:
10
AN:
249790
Hom.:
0
AF XY:
0.0000369
AC XY:
5
AN XY:
135528
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000233
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:
0.00000883
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1459668
Hom.:
0
Cov.:
30
AF XY:
0.0000124
AC XY:
9
AN XY:
726254
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000202
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:
0.00000450
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.0000189
ExAC
AF:
0.0000330
AC:
4

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 01, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.185C>G (p.P62R) alteration is located in exon 3 (coding exon 3) of the ZNF429 gene. This alteration results from a C to G substitution at nucleotide position 185, causing the proline (P) at amino acid position 62 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
0.18
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.10
T;.;.
Eigen
Benign
-0.31
Eigen_PC
Benign
-0.68
FATHMM_MKL
Benign
0.020
N
LIST_S2
Benign
0.58
T;T;T
M_CAP
Benign
0.0013
T
MetaRNN
Benign
0.15
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.6
M;.;.
PrimateAI
Benign
0.30
T
PROVEAN
Pathogenic
-5.9
D;.;.
REVEL
Benign
0.024
Sift
Pathogenic
0.0
D;.;.
Sift4G
Uncertain
0.0080
D;D;D
Polyphen
0.99
D;.;.
Vest4
0.16
MutPred
0.36
Loss of catalytic residue at P62 (P = 0.0083);Loss of catalytic residue at P62 (P = 0.0083);Loss of catalytic residue at P62 (P = 0.0083);
MVP
0.58
MPC
0.21
ClinPred
0.42
T
GERP RS
0.23
Varity_R
0.22
gMVP
0.020

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: rs375122896; hg19: chr19-21713445; API