dbSNP rs1312663563: ZNF18:p.Pro256Leu (chr17-11983392-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001303281.2(ZNF18):c.767C>T(p.Pro256Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,564 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ZNF18
NM_001303281.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.25

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14183801).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF18	NM_001303281.2	MANE Select	c.767C>T	p.Pro256Leu	missense	Exon 6 of 7	NP_001290210.1	P17022-1
ZNF18	NM_144680.4		c.767C>T	p.Pro256Leu	missense	Exon 8 of 9	NP_653281.2	P17022-1
ZNF18	NM_001303282.2		c.764C>T	p.Pro255Leu	missense	Exon 6 of 7	NP_001290211.1	P17022-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZNF18	ENST00000580306.7	TSL:2 MANE Select	c.767C>T	p.Pro256Leu	missense	Exon 6 of 7	ENSP00000463471.1	P17022-1
ZNF18	ENST00000580613.5	TSL:1	c.767C>T	p.Pro256Leu	missense	Exon 5 of 6	ENSP00000462296.3	P17022-1
ZNF18	ENST00000454073.7	TSL:1	c.764C>T	p.Pro255Leu	missense	Exon 6 of 7	ENSP00000391376.3	P17022-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000400

AC:

AN:

250294

AF XY:

0.00000739

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461564

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727110

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33470

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111752

Other (OTH)

AF:

0.00

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.21

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.35

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.45

M_CAP

Benign

0.010

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.4

PhyloP100

5.3

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.092

Sift

Uncertain

0.0030

Sift4G

Benign

0.63

Polyphen

0.0080

Vest4

0.24

MutPred

0.32

Loss of disorder (P = 0.0411)

MVP

0.36

MPC

0.19

ClinPred

0.40

GERP RS

3.6

Varity_R

0.091

gMVP

0.21

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over