Variant 11-9472706-G-A 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.142G>A(p.Val48Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000756 in 1,454,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 32)

Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

ZNF143
NM_003442.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.25

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:

ZNF143 (HGNC:):

ZNF143 links:

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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=0.22317082).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF143	NM_003442.6 linkuse as main transcript	c.142G>A	p.Val48Ile	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 linkuse as main transcript	c.142G>A	p.Val48Ile	missense_variant	3/16	1	NM_003442.6	ENSP00000379847.2		P52747-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000123

AC:

AN:

243872

Hom.:

AF XY:

0.0000152

AC XY:

AN XY:

131978

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000559

Gnomad SAS exome

AF:

0.0000345

Gnomad FIN exome

AF:

0.0000467

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000756

AC:

AN:

1454948

Hom.:

Cov.:

AF XY:

0.00000829

AC XY:

AN XY:

723876

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.00000541

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

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

Aug 14, 2024

The c.142G>A (p.V48I) alteration is located in exon 3 (coding exon 2) of the ZNF143 gene. This alteration results from a G to A substitution at nucleotide position 142, causing the valine (V) at amino acid position 48 to be replaced by an isoleucine (I). 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

0.083

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

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

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

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

M_CAP

Benign

0.0050

MetaRNN

Benign

0.22

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

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

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.14

N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.069

Sift

Benign

0.038

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

Sift4G

Benign

0.30

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

Polyphen

0.091

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

Vest4

0.52, 0.53, 0.51

MutPred

0.28

Loss of catalytic residue at V48 (P = 0.0104);Loss of catalytic residue at V48 (P = 0.0104);Loss of catalytic residue at V48 (P = 0.0104);Loss of catalytic residue at V48 (P = 0.0104);Loss of catalytic residue at V48 (P = 0.0104);Loss of catalytic residue at V48 (P = 0.0104);Loss of catalytic residue at V48 (P = 0.0104);Loss of catalytic residue at V48 (P = 0.0104);Loss of catalytic residue at V48 (P = 0.0104);Loss of catalytic residue at V48 (P = 0.0104);Loss of catalytic residue at V48 (P = 0.0104);Loss of catalytic residue at V48 (P = 0.0104);

MVP

0.61

MPC

0.37

ClinPred

0.43

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.050

gMVP

0.16

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