Variant 19-12015059-G-A 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_001308348.2(ZNF433):c.1799C>T(p.Ser600Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00011 in 1,613,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

ZNF433
NM_001308348.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.636

Variant links:

Genes affected

ZNF433 (HGNC:20811): (zinc finger protein 433) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription 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]

ZNF433 links:

ZNF433-AS1 (HGNC:53776): (ZNF433 and ZNF878 antisense RNA 1)

ZNF433-AS1 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=0.025181383).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF433	NM_001308348.2 linkuse as main transcript	c.1799C>T	p.Ser600Leu	missense_variant	4/4	ENST00000550507.7
ZNF433-AS1	NR_134928.1 linkuse as main transcript	n.256+13237G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF433	ENST00000550507.7 linkuse as main transcript	c.1799C>T	p.Ser600Leu	missense_variant	4/4	2	NM_001308348.2	A2
ZNF433-AS1	ENST00000476474.5 linkuse as main transcript	n.194+13237G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000106

AC:

AN:

151552

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.000390

Gnomad SAS

AF:

0.000209

Gnomad FIN

AF:

0.0000950

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000481

GnomAD3 exomes

AF:

0.000223

AC:

AN:

250754

Hom.:

AF XY:

0.000221

AC XY:

AN XY:

135788

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00219

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.000329

GnomAD4 exome

AF:

0.000110

AC:

161

AN:

1461830

Hom.:

Cov.:

AF XY:

0.000120

AC XY:

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00272

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000290

Gnomad4 FIN exome

AF:

0.000318

Gnomad4 NFE exome

AF:

0.0000279

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000105

AC:

AN:

151670

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74104

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.000391

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.0000950

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000476

Alfa

AF:

0.000314

Hom.:

Bravo

AF:

0.0000793

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000181

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000296

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

Apr 07, 2022

The c.1808C>T (p.S603L) alteration is located in exon 4 (coding exon 4) of the ZNF433 gene. This alteration results from a C to T substitution at nucleotide position 1808, causing the serine (S) at amino acid position 603 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

0.53

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.47

T;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.025

T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-3.9

D;D

REVEL

Benign

0.060

Sift

Uncertain

0.022

D;D

Sift4G

Uncertain

0.013

D;D

Polyphen

0.99

.;D

Vest4

0.22

MVP

0.39

MPC

0.052

ClinPred

0.14

GERP RS

0.82

Varity_R

0.14

gMVP

0.0078

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