Variant 11-9472731-C-G 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_003442.6(ZNF143):c.167C>G(p.Ala56Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000258 in 1,602,498 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.00019 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 0 hom. )

Consequence

ZNF143
NM_003442.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.58

Variant links:

Genes affected

ZNF143 (HGNC:12928): (zinc finger protein 143) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in positive regulation of snRNA transcription by RNA polymerase II. Predicted to be located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF143 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=0.21176735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF143	NM_003442.6 link	c.167C>G	p.Ala56Gly	missense_variant	3/16	ENST00000396602.7	NP_003433.3	P52747-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF143	ENST00000396602.7 link	c.167C>G	p.Ala56Gly	missense_variant	3/16	1	NM_003442.6	ENSP00000379847.2		P52747-1

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000367

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000146

AC:

AN:

239116

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

129534

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:

0.000178

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000274

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000265

AC:

384

AN:

1450364

Hom.:

Cov.:

AF XY:

0.000259

AC XY:

187

AN XY:

721564

show subpopulations

Gnomad4 AFR exome

AF:

0.0000306

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000178

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000319

Gnomad4 OTH exome

AF:

0.000217

GnomAD4 genome

AF:

0.000191

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000367

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000294

Hom.:

Bravo

AF:

0.000162

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000699

AC:

ExAC

AF:

0.000107

AC:

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

Mar 31, 2023

The c.167C>G (p.A56G) alteration is located in exon 3 (coding exon 2) of the ZNF143 gene. This alteration results from a C to G substitution at nucleotide position 167, causing the alanine (A) at amino acid position 56 to be replaced by a glycine (G). 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

0.17

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.035

T;.;T;.;.;.;T;T;.;.;T;T

Eigen

Benign

0.059

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.75

T;.;T;T;T;T;T;T;T;T;D;D

M_CAP

Benign

0.0059

MetaRNN

Benign

0.21

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

.;L;L;L;.;.;.;.;.;.;.;.

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-2.0

N;N;N;N;N;N;N;N;N;N;N;D

REVEL

Benign

0.14

Sift

Benign

0.039

D;D;D;D;D;D;D;D;T;D;T;T

Sift4G

Benign

0.13

T;T;D;T;T;T;D;T;T;T;T;T

Polyphen

0.037

.;.;B;.;.;.;.;.;.;.;.;.

Vest4

0.57, 0.57, 0.61

MVP

0.65

MPC

0.47

ClinPred

0.070

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.19

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