chr17-11978468-C-T

Variant names:

• chr17-11978468-C-T
• rs140193484
• NM_001303281.2:c.1139G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001303281.2(ZNF18):​c.1139G>A​(p.Gly380Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00059 in 1,585,946 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00039 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00061 (0 hom.)
• Consequence: ZNF18 NM_001303281.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.06
• Publications: 3 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.026671797).

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.1139G>A	p.Gly380Glu	missense	Exon 7 of 7	NP_001290210.1	P17022-1
	ZNF18	NM_144680.4		c.1139G>A	p.Gly380Glu	missense	Exon 9 of 9	NP_653281.2	P17022-1
	ZNF18	NM_001303282.2		c.1136G>A	p.Gly379Glu	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.1139G>A	p.Gly380Glu	missense	Exon 7 of 7	ENSP00000463471.1	P17022-1
	ZNF18	ENST00000580613.5	TSL:1	c.1139G>A	p.Gly380Glu	missense	Exon 6 of 6	ENSP00000462296.3	P17022-1
	ZNF18	ENST00000454073.7	TSL:1	c.1136G>A	p.Gly379Glu	missense	Exon 7 of 7	ENSP00000391376.3	P17022-2

Frequencies

GnomAD3 genomes AF: 0.000394 AC: 60 AN: 152206 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000406 AC: 93 AN: 228896 AF XY: 0.000390

Gnomad AFR exome AF: 0.0000626

Gnomad AMR exome AF: 0.000193

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000297

Gnomad NFE exome AF: 0.000732

Gnomad OTH exome AF: 0.000552

GnomAD4 exome AF: 0.000610 AC: 875 AN: 1433740 Hom.: 0 Cov.: 31 AF XY: 0.000588 AC XY: 418 AN XY: 710740

African (AFR) AF: 0.0000618 AC: 2 AN: 32386

American (AMR) AF: 0.000221 AC: 9 AN: 40782

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23964

East Asian (EAS) AF: 0.00 AC: 0 AN: 39486

South Asian (SAS) AF: 0.00 AC: 0 AN: 81310

European-Finnish (FIN) AF: 0.000191 AC: 10 AN: 52328

Middle Eastern (MID) AF: 0.000179 AC: 1 AN: 5588

European-Non Finnish (NFE) AF: 0.000753 AC: 827 AN: 1098898

Other (OTH) AF: 0.000441 AC: 26 AN: 58998

GnomAD4 genome AF: 0.000394 AC: 60 AN: 152206 Hom.: 1 Cov.: 32 AF XY: 0.000309 AC XY: 23 AN XY: 74362

African (AFR) AF: 0.000145 AC: 6 AN: 41454

American (AMR) AF: 0.000523 AC: 8 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000647 AC: 44 AN: 68038

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.000601 Hom.: 0

Bravo AF: 0.000370

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.000387 AC: 47

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	Benign	0.12
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	12
DANN	Benign	0.46
DEOGEN2	Benign	0.069	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.065	N
PhyloP100		2.1
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.12
Sift	Benign	0.32	T
Sift4G	Benign	0.68	T
Polyphen		0.0010	B
Vest4		0.13
MVP		0.15
MPC		0.23
ClinPred		0.022	T
GERP RS		-1.3
Varity_R		0.038
gMVP		0.18
Mutation Taster		=100/0	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: rs140193484; hg19: chr17-11881785;