Variant 19-44150458-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000426739.7(ZNF234):c.188A>G(p.Lys63Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,590,556 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: 𝑓 0.000099 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

ZNF234
ENST00000426739.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.128

Variant links:

Genes affected

ZNF234 (HGNC:13027): (zinc finger protein 234) 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]

ZNF234 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.036566615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF234	NM_006630.3 linkuse as main transcript	c.188A>G	p.Lys63Arg	missense_variant	5/6	ENST00000426739.7	NP_006621.1	Q14588A0A024R0N3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF234	ENST00000426739.7 linkuse as main transcript	c.188A>G	p.Lys63Arg	missense_variant	5/6	1	NM_006630.3	ENSP00000400878.1	Q14588
ZNF234	ENST00000592437.5 linkuse as main transcript	c.188A>G	p.Lys63Arg	missense_variant	5/6	1		ENSP00000465011.1	Q14588
ZNF234	ENST00000590795.1 linkuse as main transcript	n.*232A>G		non_coding_transcript_exon_variant	6/6	3		ENSP00000466129.1	K7ELL2
ZNF234	ENST00000590795.1 linkuse as main transcript	n.*232A>G		3_prime_UTR_variant	6/6	3		ENSP00000466129.1	K7ELL2

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000939

AC:

AN:

213072

Hom.:

AF XY:

0.000114

AC XY:

AN XY:

114282

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000663

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000382

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000182

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000132

AC:

190

AN:

1438368

Hom.:

Cov.:

AF XY:

0.000143

AC XY:

102

AN XY:

713014

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000489

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000364

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000163

Gnomad4 OTH exome

AF:

0.000101

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000180

Hom.:

Bravo

AF:

0.0000982

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.0000415

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

Aug 21, 2023

The c.188A>G (p.K63R) alteration is located in exon 5 (coding exon 3) of the ZNF234 gene. This alteration results from a A to G substitution at nucleotide position 188, causing the lysine (K) at amino acid position 63 to be replaced by an arginine (R). 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

0.071

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0043

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.018

LIST_S2

Benign

0.046

.;T

M_CAP

Benign

0.0011

MetaRNN

Benign

0.037

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.41

N;N

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.36

.;N

REVEL

Benign

0.015

Sift

Benign

0.031

.;D

Sift4G

Benign

0.34

T;T

Polyphen

0.0

B;B

Vest4

0.11

MVP

0.18

MPC

0.082

ClinPred

0.027

GERP RS

-2.9

Varity_R

0.041

gMVP

0.013

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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