Variant chr19-58067248-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_001289401.2(ZNF135):c.764C>T(p.Ser255Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,614,166 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 3 hom. )

Consequence

ZNF135
NM_001289401.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.110

Variant links:

Genes affected

ZNF135 (HGNC:12919): (zinc finger protein 135) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in cytoskeleton organization and regulation of cell morphogenesis. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF135 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=0.020501286).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF135	NM_001289401.2 linkuse as main transcript	c.764C>T	p.Ser255Leu	missense_variant	5/5	ENST00000313434.10	NP_001276330.1	P52742-1Q8N9M3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF135	ENST00000313434.10 linkuse as main transcript	c.764C>T	p.Ser255Leu	missense_variant	5/5	1	NM_001289401.2	ENSP00000321406.5		P52742-1

Frequencies

GnomAD3 genomes

AF:

0.000519

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000955

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000533

AC:

134

AN:

251396

Hom.:

AF XY:

0.000500

AC XY:

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00104

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.00116

AC:

1697

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

826

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00148

Gnomad4 OTH exome

AF:

0.000464

GnomAD4 genome

AF:

0.000519

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000956

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00105

Hom.:

Bravo

AF:

0.000548

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000486

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000818

EpiControl

AF:

0.000771

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

Oct 06, 2021

The c.836C>T (p.S279L) alteration is located in exon 4 (coding exon 4) of the ZNF135 gene. This alteration results from a C to T substitution at nucleotide position 836, causing the serine (S) at amino acid position 279 to be replaced by a leucine (L). 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

Uncertain

0.55

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.50

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.097

.;.;T;.;T

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.81

T;T;T;T;T

M_CAP

Benign

0.0076

MetaRNN

Benign

0.021

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

.;.;M;.;.

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.2

D;D;D;D;D

REVEL

Benign

0.093

Sift

Benign

0.059

T;T;T;T;T

Sift4G

Uncertain

0.021

D;D;D;T;D

Polyphen

0.99

.;.;D;.;.

Vest4

0.34

MVP

0.21

MPC

0.37

ClinPred

0.041

GERP RS

2.5

Varity_R

0.16

gMVP

0.075

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