Variant 8-144774295-C-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_001286769.2(ZNF34):c.591G>C(p.Arg197Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,460,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: not found (cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

ZNF34
NM_001286769.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.27

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:

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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=0.059875846).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF34	NM_001286769.2 linkuse as main transcript	c.591G>C	p.Arg197Ser	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.591G>C	p.Arg197Ser	missense_variant	6/6	1	NM_001286769.2	ENSP00000396894.2	A0A0C4DG42
ZNF34	ENST00000343459.8 linkuse as main transcript	c.654G>C	p.Arg218Ser	missense_variant	6/6	1		ENSP00000341528.5	Q8IZ26
ZNF34	ENST00000534337.6 linkuse as main transcript	c.471G>C	p.Arg157Ser	missense_variant	4/4	3		ENSP00000434049.2	E9PSD0
ZNF34	ENST00000527740.1 linkuse as main transcript	n.881G>C		non_coding_transcript_exon_variant	4/4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000405

AC:

AN:

246810

Hom.:

AF XY:

0.00000746

AC XY:

AN XY:

134006

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000896

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1460796

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726634

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:

0.00000720

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Nov 07, 2024

The c.654G>C (p.R218S) alteration is located in exon 6 (coding exon 5) of the ZNF34 gene. This alteration results from a G to C substitution at nucleotide position 654, causing the arginine (R) at amino acid position 218 to be replaced by a serine (S). 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

0.21

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.015

T;T;T

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.16

T;T;T

M_CAP

Benign

0.0099

MetaRNN

Benign

0.060

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.23

N;.;.

PrimateAI

Benign

0.24

PROVEAN

Benign

0.62

N;N;N

REVEL

Benign

0.10

Sift

Benign

0.067

T;T;T

Sift4G

Benign

0.10

T;T;.

Polyphen

0.44

B;.;.

Vest4

0.12

MutPred

0.31

Gain of phosphorylation at R218 (P = 0.025);.;.;

MVP

0.50

MPC

0.33

ClinPred

0.15

GERP RS

0.70

Varity_R

0.13

gMVP

0.17

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