19-58084729-C-A

Variant names:

Variant summary

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

The NM_001145543.2(ZSCAN18):c.1489G>T(p.Val497Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000218 in 1,376,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. V497M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

ZSCAN18
NM_001145543.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.735

Publications

0 publications found

Variant links:

Genes affected

ZSCAN18 (HGNC:21037): (zinc finger and SCAN domain containing 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]

ZSCAN18 links:

ZNF135 (HGNC:12919): (zinc finger protein 135) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in cytoskeleton organization and regulation of cell morphogenesis. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF135 links:

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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=0.08896181).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145543.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZSCAN18	NM_001145543.2	MANE Select	c.1489G>T	p.Val497Leu	missense	Exon 7 of 7	NP_001139015.1	Q8TBC5-1
ZSCAN18	NM_001145542.1		c.1657G>T	p.Val553Leu	missense	Exon 7 of 7	NP_001139014.1	Q8TBC5-3
ZSCAN18	NM_023926.5		c.1489G>T	p.Val497Leu	missense	Exon 7 of 7	NP_076415.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZSCAN18	ENST00000601144.6	TSL:1 MANE Select	c.1489G>T	p.Val497Leu	missense	Exon 7 of 7	ENSP00000468934.1	Q8TBC5-1
ZSCAN18	ENST00000240727.10	TSL:1	c.1489G>T	p.Val497Leu	missense	Exon 7 of 7	ENSP00000240727.5	Q8TBC5-1
ZSCAN18	ENST00000433686.6	TSL:1	c.1180G>T	p.Val394Leu	missense	Exon 6 of 6	ENSP00000412253.2	A0A0C4DG78

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000218

AC:

AN:

1376976

Hom.:

Cov.:

AF XY:

0.00000441

AC XY:

AN XY:

679588

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

30896

American (AMR)

AF:

0.00

AC:

AN:

33504

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21612

East Asian (EAS)

AF:

0.00

AC:

AN:

38520

South Asian (SAS)

AF:

0.0000133

AC:

AN:

74968

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35110

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5392

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1080058

Other (OTH)

AF:

0.0000351

AC:

AN:

56916

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0225104), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.041

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.012

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.43

M_CAP

Benign

0.0063

MetaRNN

Benign

0.089

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.81

PhyloP100

-0.73

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.18

REVEL

Benign

0.043

Sift

Benign

0.17

Sift4G

Benign

0.27

Polyphen

0.0040

Vest4

0.060

MutPred

0.48

Gain of glycosylation at P494 (P = 0.1658)

MVP

0.14

MPC

0.060

ClinPred

0.053

GERP RS

-6.0

Varity_R

0.048

gMVP

0.17

Mutation Taster

=100/0

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over