Variant 19-44010589-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006300.4(ZNF230):c.550C>T(p.Arg184Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000844 in 1,614,196 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00060 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00087 ( 1 hom. )

Consequence

ZNF230
NM_006300.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -6.18

Variant links:

Genes affected

ZNF230 (HGNC:13024): (zinc finger protein 230) 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]

ZNF230 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01896283).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF230	NM_006300.4 linkuse as main transcript	c.550C>T	p.Arg184Cys	missense_variant	5/5	ENST00000429154.7	NP_006291.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF230	ENST00000429154.7 linkuse as main transcript	c.550C>T	p.Arg184Cys	missense_variant	5/5	1	NM_006300.4	ENSP00000409318	P1
ZNF230	ENST00000585568.5 linkuse as main transcript	c.*460C>T		3_prime_UTR_variant, NMD_transcript_variant	5/5	5		ENSP00000465324

Frequencies

GnomAD3 genomes

AF:

0.000578

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000896

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000553

AC:

139

AN:

251410

Hom.:

AF XY:

0.000500

AC XY:

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000832

Gnomad NFE exome

AF:

0.000836

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000869

AC:

1271

AN:

1461880

Hom.:

Cov.:

AF XY:

0.000828

AC XY:

602

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.000559

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000842

Gnomad4 NFE exome

AF:

0.00102

Gnomad4 OTH exome

AF:

0.000795

GnomAD4 genome

AF:

0.000604

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.000537

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.000897

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000683

Hom.:

Bravo

AF:

0.000472

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.000453

AC:

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.000889

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

Aug 16, 2022

The c.550C>T (p.R184C) alteration is located in exon 5 (coding exon 4) of the ZNF230 gene. This alteration results from a C to T substitution at nucleotide position 550, causing the arginine (R) at amino acid position 184 to be replaced by a cysteine (C). 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

0.13

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.030

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.00015

LIST_S2

Benign

0.13

M_CAP

Benign

0.0015

MetaRNN

Benign

0.019

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

PrimateAI

Benign

0.19

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.014

Sift

Benign

0.23

Sift4G

Benign

0.18

Polyphen

0.058

Vest4

0.068

MVP

0.31

MPC

0.18

ClinPred

0.025

GERP RS

-0.23

Varity_R

0.085

gMVP

0.032

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