Variant 19-21057870-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_025189.4(ZNF430):c.1562C>G(p.Ala521Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

ZNF430
NM_025189.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.18

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]

ZNF430 links:

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=0.08590788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZNF430	NM_025189.4 linkuse as main transcript	c.1562C>G	p.Ala521Gly	missense_variant	5/5	ENST00000261560.10	NP_079465.3
ZNF430	NM_001172671.2 linkuse as main transcript	c.1559C>G	p.Ala520Gly	missense_variant	5/5		NP_001166142.1
ZNF430	XM_047439464.1 linkuse as main transcript	c.1469C>G	p.Ala490Gly	missense_variant	4/4		XP_047295420.1
ZNF430	XM_047439465.1 linkuse as main transcript	c.1466C>G	p.Ala489Gly	missense_variant	4/4		XP_047295421.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF430	ENST00000261560.10 linkuse as main transcript	c.1562C>G	p.Ala521Gly	missense_variant	5/5	1	NM_025189.4	ENSP00000261560	P1
ZNF430	ENST00000597922.1 linkuse as main transcript	c.68C>G	p.Ala23Gly	missense_variant	1/2	4		ENSP00000469787

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000478

AC:

AN:

250790

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135636

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461678

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727132

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000576

AC:

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 submitter

clinical testing

Ambry Genetics

Jan 02, 2024

The c.1562C>G (p.A521G) alteration is located in exon 5 (coding exon 5) of the ZNF430 gene. This alteration results from a C to G substitution at nucleotide position 1562, causing the alanine (A) at amino acid position 521 to be replaced by a glycine (G). 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

0.098

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.64

CADD

Benign

2.5

DANN

Benign

0.88

DEOGEN2

Benign

0.071

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0012

LIST_S2

Benign

0.44

M_CAP

Benign

0.0044

MetaRNN

Benign

0.086

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.046

Sift

Benign

0.048

Sift4G

Uncertain

0.053

Polyphen

0.0090

Vest4

0.043

MutPred

0.61

Gain of disorder (P = 0.0658);

MVP

0.25

MPC

0.14

ClinPred

0.031

GERP RS

1.0

Varity_R

0.14

gMVP

0.023

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over