chr17-11978240-C-T

Variant names:

• chr17-11978240-C-T
• rs933067074
• NM_001303281.2:c.1367G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001303281.2(ZNF18):​c.1367G>A​(p.Arg456Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,120 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZNF18 NM_001303281.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.76
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001303281.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF18	NM_001303281.2	MANE Select	c.1367G>A	p.Arg456Lys	missense	Exon 7 of 7	NP_001290210.1	P17022-1
	ZNF18	NM_144680.4		c.1367G>A	p.Arg456Lys	missense	Exon 9 of 9	NP_653281.2	P17022-1
	ZNF18	NM_001303282.2		c.1364G>A	p.Arg455Lys	missense	Exon 7 of 7	NP_001290211.1	P17022-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF18	ENST00000580306.7	TSL:2 MANE Select	c.1367G>A	p.Arg456Lys	missense	Exon 7 of 7	ENSP00000463471.1	P17022-1
	ZNF18	ENST00000580613.5	TSL:1	c.1367G>A	p.Arg456Lys	missense	Exon 6 of 6	ENSP00000462296.3	P17022-1
	ZNF18	ENST00000454073.7	TSL:1	c.1364G>A	p.Arg455Lys	missense	Exon 7 of 7	ENSP00000391376.3	P17022-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461120 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726888

African (AFR) AF: 0.0000299 AC: 1 AN: 33394

American (AMR) AF: 0.00 AC: 0 AN: 44536

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26050

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111730

Other (OTH) AF: 0.00 AC: 0 AN: 60332

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	25
DANN	Benign	0.94
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.68	N
PhyloP100		2.8
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.14
Sift	Benign	0.36	T
Sift4G	Benign	0.12	T
Polyphen		0.96	D
Vest4		0.58
MutPred		0.61		Gain of methylation at R456 (P = 0.0149)
MVP		0.24
MPC		0.64
ClinPred		0.88	D
GERP RS		5.6
Varity_R		0.32
gMVP		0.36
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs933067074; hg19: chr17-11881557;