17-11978242-C-G

Position:

• chr17-11978242-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001303281.2(ZNF18):​c.1365G>C​(p.Gln455His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF18 NM_001303281.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.03

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF18	NM_001303281.2	c.1365G>C	p.Gln455His	missense_variant	7/7	ENST00000580306.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF18	ENST00000580306.7	c.1365G>C	p.Gln455His	missense_variant	7/7	2	NM_001303281.2	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 12, 2024

The c.1365G>C (p.Q455H) alteration is located in exon 9 (coding exon 6) of the ZNF18 gene. This alteration results from a G to C substitution at nucleotide position 1365, causing the glutamine (Q) at amino acid position 455 to be replaced by a histidine (H). 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	Pathogenic	0.85
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.27	T;T;T;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.48	.;T;.;T
M_CAP	Benign	0.0085	T
MetaRNN	Uncertain	0.46	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L;L;L;.
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.4	.;.;D;.
REVEL	Benign	0.21
Sift	Uncertain	0.0020	.;.;D;.
Sift4G	Benign	0.066	T;T;T;T
Polyphen		1.0	D;D;D;D
Vest4		0.40
MutPred		0.55		Gain of catalytic residue at K453 (P = 0.0899);Gain of catalytic residue at K453 (P = 0.0899);Gain of catalytic residue at K453 (P = 0.0899);.;
MVP		0.27
MPC		0.27
ClinPred		0.96	D
GERP RS		4.6
Varity_R		0.54
gMVP		0.44

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.

Other links and lift over

hg19: chr17-11881559;