Variant 10-43557040-T-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_001099282.2(ZNF239):c.1040A>T(p.Tyr347Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,614,036 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

ZNF239
NM_001099282.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0530

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14820564).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF239	NM_001099282.2 linkuse as main transcript	c.1040A>T	p.Tyr347Phe	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.1040A>T	p.Tyr347Phe	missense_variant	4/4	1	NM_001099282.2	P1
ZNF239	ENST00000306006.10 linkuse as main transcript	c.1040A>T	p.Tyr347Phe	missense_variant	2/2	1		P1
ZNF239	ENST00000426961.1 linkuse as main transcript	c.1040A>T	p.Tyr347Phe	missense_variant	3/3	2		P1
ZNF239	ENST00000535642.5 linkuse as main transcript	c.1040A>T	p.Tyr347Phe	missense_variant	2/2	2		P1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000518

AC:

AN:

250958

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.0000626

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.0000371

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000301

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000577

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

Oct 27, 2021

The c.1040A>T (p.Y347F) alteration is located in exon 2 (coding exon 1) of the ZNF239 gene. This alteration results from a A to T substitution at nucleotide position 1040, causing the tyrosine (Y) at amino acid position 347 to be replaced by a phenylalanine (F). 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

0.19

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.52

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.24

T;T;T;T

Eigen

Benign

0.078

Eigen_PC

Benign

0.031

FATHMM_MKL

Benign

0.072

LIST_S2

Benign

0.38

.;.;.;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.36

N;N;N;N

MutationTaster

Benign

0.88

N;N;N;N;N

PrimateAI

Uncertain

0.74

PROVEAN

Uncertain

-3.5

D;D;D;D

REVEL

Benign

0.080

Sift

Benign

0.12

T;T;T;T

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.25

MutPred

0.51

Loss of phosphorylation at Y347 (P = 0.0543);Loss of phosphorylation at Y347 (P = 0.0543);Loss of phosphorylation at Y347 (P = 0.0543);Loss of phosphorylation at Y347 (P = 0.0543);

MVP

0.15

MPC

0.31

ClinPred

0.45

GERP RS

3.6

Varity_R

0.26

gMVP

0.028

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