Variant 17-11984149-G-T 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_001303281.2(ZNF18):c.715C>A(p.Leu239Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,610,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ZNF18
NM_001303281.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.814

Variant links:

Genes affected

ZNF18 (HGNC:12969): (zinc finger protein 18) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF18 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=0.10413307).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF18	NM_001303281.2 linkuse as main transcript	c.715C>A	p.Leu239Ile	missense_variant	5/7	ENST00000580306.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF18	ENST00000580306.7 linkuse as main transcript	c.715C>A	p.Leu239Ile	missense_variant	5/7	2	NM_001303281.2	P4	P17022-1

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

149976

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:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460846

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726794

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000133

AC:

AN:

149976

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

72998

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:

0.0000295

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

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

Sep 29, 2023

The c.715C>A (p.L239I) alteration is located in exon 7 (coding exon 4) of the ZNF18 gene. This alteration results from a C to A substitution at nucleotide position 715, causing the leucine (L) at amino acid position 239 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

0.15

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.035

T;T;T;.;T

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.73

.;T;.;T;T

M_CAP

Benign

0.0037

MetaRNN

Benign

0.10

T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.22

N;N;N;N;.

MutationTaster

Benign

0.99

N;N;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

0.080

.;.;N;N;.

REVEL

Benign

0.095

Sift

Benign

0.057

.;.;T;T;.

Sift4G

Benign

0.63

T;T;T;T;.

Polyphen

0.30

B;B;B;B;.

Vest4

0.42

MutPred

0.67

Gain of phosphorylation at Y236 (P = 0.123);Gain of phosphorylation at Y236 (P = 0.123);Gain of phosphorylation at Y236 (P = 0.123);Gain of phosphorylation at Y236 (P = 0.123);.;

MVP

0.19

MPC

0.22

ClinPred

0.15

GERP RS

0.97

Varity_R

0.044

gMVP

0.082

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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