Variant 19-57604375-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001321981.2(ZNF530):c.30G>C(p.Met10Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZNF530
NM_001321981.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.95

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.761

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF530	NM_001321981.2 link	c.30G>C	p.Met10Ile	missense_variant	3/4	ENST00000597700.6	NP_001308910.1	Q6P9A1M0R1P0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF530	ENST00000597700.6 link	c.30G>C	p.Met10Ile	missense_variant	3/4	2	NM_001321981.2	ENSP00000472024.2	M0R1P0
ZNF530	ENST00000332854.11 link	c.129G>C	p.Met43Ile	missense_variant	2/3	1		ENSP00000332861.5	Q6P9A1
ZNF530	ENST00000600619.1 link	n.129G>C		non_coding_transcript_exon_variant	2/4	1		ENSP00000472564.1	Q6P9A1
ZNF530	ENST00000597864.1 link	c.30G>C	p.Met10Ile	missense_variant	3/4	2		ENSP00000471527.1	M0R0Y5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461678

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727156

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 06, 2023

The c.129G>C (p.M43I) alteration is located in exon 2 (coding exon 2) of the ZNF530 gene. This alteration results from a G to C substitution at nucleotide position 129, causing the methionine (M) at amino acid position 43 to be replaced by an isoleucine (I). 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

0.94

BayesDel_addAF

Benign

-0.072

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

.;T;.

Eigen

Uncertain

0.37

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.85

T;.;T

M_CAP

Benign

0.0042

MetaRNN

Pathogenic

0.76

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.5

.;M;.

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.5

.;D;.

REVEL

Benign

0.18

Sift

Uncertain

0.0010

.;D;.

Sift4G

Uncertain

0.0070

D;D;.

Polyphen

0.99

.;D;.

Vest4

0.57, 0.41

MutPred

0.77

.;Loss of catalytic residue at M43 (P = 0.043);.;

MVP

0.20

MPC

0.56

ClinPred

0.96

GERP RS

2.0

Varity_R

0.62

gMVP

0.33

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over