chr17-11978738-C-G

Variant names:

• chr17-11978738-C-G
• rs546049246
• NM_001303281.2:c.869G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001303281.2(ZNF18):​c.869G>C​(p.Arg290Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000252 in 1,584,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R290I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: ZNF18 NM_001303281.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.382
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.09894672).

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.869G>C	p.Arg290Thr	missense	Exon 7 of 7	NP_001290210.1	P17022-1
	ZNF18	NM_144680.4		c.869G>C	p.Arg290Thr	missense	Exon 9 of 9	NP_653281.2	P17022-1
	ZNF18	NM_001303282.2		c.866G>C	p.Arg289Thr	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.869G>C	p.Arg290Thr	missense	Exon 7 of 7	ENSP00000463471.1	P17022-1
	ZNF18	ENST00000580613.5	TSL:1	c.869G>C	p.Arg290Thr	missense	Exon 6 of 6	ENSP00000462296.3	P17022-1
	ZNF18	ENST00000454073.7	TSL:1	c.866G>C	p.Arg289Thr	missense	Exon 7 of 7	ENSP00000391376.3	P17022-2

Frequencies

GnomAD3 genomes AF: 0.000106 AC: 16 AN: 151288 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000389

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000267 AC: 6 AN: 224326 AF XY: 0.0000324

Gnomad AFR exome AF: 0.000284

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000190

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000167 AC: 24 AN: 1433036 Hom.: 0 Cov.: 30 AF XY: 0.0000154 AC XY: 11 AN XY: 712728

African (AFR) AF: 0.000614 AC: 20 AN: 32558

American (AMR) AF: 0.00 AC: 0 AN: 41382

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24990

East Asian (EAS) AF: 0.00 AC: 0 AN: 39534

South Asian (SAS) AF: 0.00 AC: 0 AN: 84080

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5434

European-Non Finnish (NFE) AF: 0.00000362 AC: 4 AN: 1104422

Other (OTH) AF: 0.00 AC: 0 AN: 59398

GnomAD4 genome AF: 0.000106 AC: 16 AN: 151396 Hom.: 0 Cov.: 32 AF XY: 0.0000677 AC XY: 5 AN XY: 73904

African (AFR) AF: 0.000388 AC: 16 AN: 41232

American (AMR) AF: 0.00 AC: 0 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.00 AC: 0 AN: 4788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67956

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000868 Hom.: 0

ExAC AF: 0.0000167 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	20
DANN	Benign	0.92
DEOGEN2	Benign	0.046	T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.38
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.21
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.047	D
Polyphen		1.0	D
Vest4		0.19
MutPred		0.44		Loss of catalytic residue at R290 (P = 0.0154)
MVP		0.32
MPC		0.65
ClinPred		0.22	T
GERP RS		5.4
Varity_R		0.16
gMVP		0.49
Mutation Taster		=65/35	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: rs546049246; hg19: chr17-11882055;