Variant 19-57604371-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001321981.2(ZNF530):c.26T>C(p.Val9Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,740 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 1 hom. )

Consequence

ZNF530
NM_001321981.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.13

Variant links:

Genes affected

ZNF530 (HGNC:29297): (zinc finger protein 530) 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]

ZNF530 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF530	NM_001321981.2 linkuse as main transcript	c.26T>C	p.Val9Ala	missense_variant	3/4	ENST00000597700.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ZNF530	ENST00000597700.6 linkuse as main transcript	c.26T>C	p.Val9Ala	missense_variant	3/4	2	NM_001321981.2
ZNF530	ENST00000332854.11 linkuse as main transcript	c.125T>C	p.Val42Ala	missense_variant	2/3	1		P1
ZNF530	ENST00000600619.1 linkuse as main transcript	c.125T>C	p.Val42Ala	missense_variant, NMD_transcript_variant	2/4	1
ZNF530	ENST00000597864.1 linkuse as main transcript	c.26T>C	p.Val9Ala	missense_variant	3/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251214

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135776

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

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:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461740

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000335

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000412

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 31, 2022

The c.125T>C (p.V42A) alteration is located in exon 2 (coding exon 2) of the ZNF530 gene. This alteration results from a T to C substitution at nucleotide position 125, causing the valine (V) at amino acid position 42 to be replaced by an alanine (A). 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

0.71

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.89

Eigen

Uncertain

0.34

Eigen_PC

Benign

0.069

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.78

T;.;T

M_CAP

Benign

0.0052

MetaRNN

Uncertain

0.63

D;D;D

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.99

PrimateAI

Uncertain

0.52

Sift4G

Pathogenic

0.0

D;D;.

Polyphen

0.99

.;D;.

Vest4

0.58, 0.56

MutPred

0.80

.;Loss of stability (P = 0.0478);.;

MVP

0.27

MPC

0.52

ClinPred

0.47

GERP RS

2.0

Varity_R

0.35

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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