19-21057528-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_025189.4(ZNF430):​c.1220G>T​(p.Gly407Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

ZNF430
NM_025189.4 missense

Scores

4
2
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.475
Variant links:
Genes affected
ZNF430 (HGNC:20808): (zinc finger protein 430) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in substantia nigra development. Predicted to be located 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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.35876006).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZNF430NM_025189.4 linkuse as main transcriptc.1220G>T p.Gly407Val missense_variant 5/5 ENST00000261560.10 NP_079465.3
ZNF430NM_001172671.2 linkuse as main transcriptc.1217G>T p.Gly406Val missense_variant 5/5 NP_001166142.1
ZNF430XM_047439464.1 linkuse as main transcriptc.1127G>T p.Gly376Val missense_variant 4/4 XP_047295420.1
ZNF430XM_047439465.1 linkuse as main transcriptc.1124G>T p.Gly375Val missense_variant 4/4 XP_047295421.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZNF430ENST00000261560.10 linkuse as main transcriptc.1220G>T p.Gly407Val missense_variant 5/51 NM_025189.4 ENSP00000261560 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 10, 2023The c.1220G>T (p.G407V) alteration is located in exon 5 (coding exon 5) of the ZNF430 gene. This alteration results from a G to T substitution at nucleotide position 1220, causing the glycine (G) at amino acid position 407 to be replaced by a valine (V). 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
0.67
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.21
T
Eigen
Benign
-0.12
Eigen_PC
Benign
-0.47
FATHMM_MKL
Benign
0.28
N
LIST_S2
Benign
0.047
T
M_CAP
Benign
0.0012
T
MetaRNN
Benign
0.36
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
3.5
M
MutationTaster
Benign
0.94
D
PrimateAI
Benign
0.29
T
PROVEAN
Pathogenic
-8.5
D
REVEL
Benign
0.074
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.0040
D
Polyphen
1.0
D
Vest4
0.21
MutPred
0.63
Loss of disorder (P = 0.0476);
MVP
0.21
MPC
0.67
ClinPred
0.94
D
GERP RS
-0.11
Varity_R
0.63
gMVP
0.16

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: chr19-21240334; API