Variant 17-11978405-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_001303281.2(ZNF18):c.1202C>T(p.Ala401Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000718 in 1,393,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

ZNF18
NM_001303281.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.788

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:

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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=0.11732328).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF18	NM_001303281.2 linkuse as main transcript	c.1202C>T	p.Ala401Val	missense_variant	7/7	ENST00000580306.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF18	ENST00000580306.7 linkuse as main transcript	c.1202C>T	p.Ala401Val	missense_variant	7/7	2	NM_001303281.2	P4	P17022-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.18e-7

AC:

AN:

1393314

Hom.:

Cov.:

AF XY:

0.00000146

AC XY:

AN XY:

686764

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:

9.24e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 09, 2023

The c.1202C>T (p.A401V) alteration is located in exon 9 (coding exon 6) of the ZNF18 gene. This alteration results from a C to T substitution at nucleotide position 1202, causing the alanine (A) at amino acid position 401 to be replaced by a valine (V). 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

0.13

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.024

T;T;T;.;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.12

.;T;.;T;T

M_CAP

Benign

0.0065

MetaRNN

Benign

0.12

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Uncertain

2.1

M;M;M;.;.

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.51

.;.;N;.;.

REVEL

Benign

0.070

Sift

Benign

0.16

.;.;T;.;.

Sift4G

Benign

0.097

T;T;T;T;.

Polyphen

0.43

B;B;B;P;.

Vest4

0.19

MutPred

0.36

Loss of glycosylation at P402 (P = 0.0863);Loss of glycosylation at P402 (P = 0.0863);Loss of glycosylation at P402 (P = 0.0863);.;.;

MVP

0.42

MPC

0.26

ClinPred

0.73

GERP RS

5.8

Varity_R

0.092

gMVP

0.21

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over