Variant 10-43557089-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001099282.2(ZNF239):c.991C>T(p.Arg331Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000811 in 1,602,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

ZNF239
NM_001099282.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.258

Variant links:

Genes affected

ZNF239 (HGNC:13031): (zinc finger protein 239) MOK2 proteins are DNA- and RNA-binding proteins that are mainly associated with nuclear RNP components, including the nucleoli and extranucleolar structures (Arranz et al., 1997 [PubMed 9121460]).[supplied by OMIM, Mar 2008]

ZNF239 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27981064).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF239	NM_001099282.2 linkuse as main transcript	c.991C>T	p.Arg331Cys	missense_variant	4/4	ENST00000374446.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ZNF239	ENST00000374446.7 linkuse as main transcript	c.991C>T	p.Arg331Cys	missense_variant	4/4	1	NM_001099282.2	P1
ZNF239	ENST00000306006.10 linkuse as main transcript	c.991C>T	p.Arg331Cys	missense_variant	2/2	1		P1
ZNF239	ENST00000426961.1 linkuse as main transcript	c.991C>T	p.Arg331Cys	missense_variant	3/3	2		P1
ZNF239	ENST00000535642.5 linkuse as main transcript	c.991C>T	p.Arg331Cys	missense_variant	2/2	2		P1

Frequencies

GnomAD3 genomes

AF:

0.0000141

AC:

AN:

141408

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000153

Gnomad OTH

AF:

0.000515

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250686

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135700

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1460818

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726708

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000141

AC:

AN:

141408

Hom.:

Cov.:

AF XY:

0.0000291

AC XY:

AN XY:

68692

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000153

Gnomad4 OTH

AF:

0.000515

Alfa

AF:

0.0000501

Hom.:

Bravo

AF:

0.0000227

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Dec 01, 2022

The c.991C>T (p.R331C) alteration is located in exon 2 (coding exon 1) of the ZNF239 gene. This alteration results from a C to T substitution at nucleotide position 991, causing the arginine (R) at amino acid position 331 to be replaced by a cysteine (C). 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

0.27

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.17

T;T;T;T

Eigen

Benign

0.16

Eigen_PC

Benign

0.10

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.84

.;.;.;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.28

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

2.0

M;M;M;M

MutationTaster

Benign

0.98

D;D;D;D;D

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-2.9

D;D;D;D

REVEL

Benign

0.17

Sift

Benign

0.032

D;D;D;D

Sift4G

Uncertain

0.035

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.42

MutPred

0.27

Loss of MoRF binding (P = 0.0199);Loss of MoRF binding (P = 0.0199);Loss of MoRF binding (P = 0.0199);Loss of MoRF binding (P = 0.0199);

MVP

0.42

MPC

0.36

ClinPred

0.91

GERP RS

3.8

Varity_R

0.16

gMVP

0.072

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