Variant 8-144774194-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001286769.2(ZNF34):c.692A>G(p.Tyr231Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000533 in 1,613,734 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

ZNF34
NM_001286769.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.10

Variant links:

Genes affected

ZNF34 (HGNC:13098): (zinc finger protein 34) 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. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF34 links:

ZNF34 (HGNC:):

ZNF34 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08528611).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF34	NM_001286769.2 linkuse as main transcript	c.692A>G	p.Tyr231Cys	missense_variant	6/6	ENST00000429371.7	NP_001273698.1	Q8IZ26A0A0C4DG42

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZNF34	ENST00000429371.7 linkuse as main transcript	c.692A>G	p.Tyr231Cys	missense_variant	6/6	1	NM_001286769.2	ENSP00000396894.2	A0A0C4DG42
ZNF34	ENST00000343459.8 linkuse as main transcript	c.755A>G	p.Tyr252Cys	missense_variant	6/6	1		ENSP00000341528.5	Q8IZ26
ZNF34	ENST00000534337.6 linkuse as main transcript	c.572A>G	p.Tyr191Cys	missense_variant	4/4	3		ENSP00000434049.2	E9PSD0
ZNF34	ENST00000527740.1 linkuse as main transcript	n.982A>G		non_coding_transcript_exon_variant	4/4	5

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000280

AC:

AN:

249602

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135400

show subpopulations

Gnomad AFR exome

AF:

0.0000645

Gnomad AMR exome

AF:

0.00

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:

0.0000531

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000554

AC:

AN:

1461706

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000684

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152028

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000386

Hom.:

Bravo

AF:

0.0000491

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000353

AC:

ExAC

AF:

0.0000330

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Sep 10, 2024

The c.755A>G (p.Y252C) alteration is located in exon 6 (coding exon 5) of the ZNF34 gene. This alteration results from a A to G substitution at nucleotide position 755, causing the tyrosine (Y) at amino acid position 252 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

0.12

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.66

CADD

Benign

1.7

DANN

Benign

0.91

DEOGEN2

Benign

0.053

T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.74

T;T;T

M_CAP

Benign

0.0012

MetaRNN

Benign

0.085

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.075

N;.;.

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.042

Sift

Benign

0.060

T;T;T

Sift4G

Uncertain

0.019

D;D;.

Polyphen

0.0010

B;.;.

Vest4

0.12

MVP

0.26

MPC

0.34

ClinPred

0.068

GERP RS

-1.7

Varity_R

0.060

gMVP

0.058

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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