Variant 19-57620639-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 NM_003435.5(ZNF134):c.520A>G(p.Met174Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000492 in 1,614,102 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00051 ( 1 hom. )

Consequence

ZNF134
NM_003435.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.128

Variant links:

Genes affected

ZNF134 (HGNC:12918): (zinc finger protein 134) Predicted to enable DNA-binding transcription repressor 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 nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF134 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=0.030164808).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF134	NM_003435.5 linkuse as main transcript	c.520A>G	p.Met174Val	missense_variant	3/3	ENST00000396161.10	NP_003426.3	P52741-1Q5U5N5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF134	ENST00000396161.10 linkuse as main transcript	c.520A>G	p.Met174Val	missense_variant	3/3	1	NM_003435.5	ENSP00000379464.4		P52741-1

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000283

AC:

AN:

250612

Hom.:

AF XY:

0.000287

AC XY:

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.0000634

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000490

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000458

Gnomad OTH exome

AF:

0.000329

GnomAD4 exome

AF:

0.000514

AC:

752

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000514

AC XY:

374

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000499

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000603

Gnomad4 OTH exome

AF:

0.000513

GnomAD4 genome

AF:

0.000276

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.000957

Alfa

AF:

0.000334

Hom.:

Bravo

AF:

0.000257

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000272

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

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

Jun 07, 2024

The c.520A>G (p.M174V) alteration is located in exon 3 (coding exon 2) of the ZNF134 gene. This alteration results from a A to G substitution at nucleotide position 520, causing the methionine (M) at amino acid position 174 to be replaced by a valine (V). 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

0.096

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.55

CADD

Benign

9.4

DANN

Benign

0.87

DEOGEN2

Benign

0.010

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.0045

LIST_S2

Benign

0.12

M_CAP

Benign

0.0046

MetaRNN

Benign

0.030

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.92

REVEL

Benign

0.043

Sift

Benign

0.21

Sift4G

Benign

0.24

Polyphen

0.0020

Vest4

0.11

MVP

0.23

MPC

0.044

ClinPred

0.011

GERP RS

3.3

Varity_R

0.19

gMVP

0.047

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