rs200085530

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001145543.2(ZSCAN18):c.1204G>C(p.Ala402Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000119 in 1,590,224 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A402T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

ZSCAN18
NM_001145543.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.058430403).

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.1204G>C	p.Ala402Pro	missense	Exon 7 of 7	NP_001139015.1	Q8TBC5-1
ZSCAN18	NM_001145542.1		c.1372G>C	p.Ala458Pro	missense	Exon 7 of 7	NP_001139014.1	Q8TBC5-3
ZSCAN18	NM_023926.5		c.1204G>C	p.Ala402Pro	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.1204G>C	p.Ala402Pro	missense	Exon 7 of 7	ENSP00000468934.1	Q8TBC5-1
ZSCAN18	ENST00000240727.10	TSL:1	c.1204G>C	p.Ala402Pro	missense	Exon 7 of 7	ENSP00000240727.5	Q8TBC5-1
ZSCAN18	ENST00000433686.6	TSL:1	c.895G>C	p.Ala299Pro	missense	Exon 6 of 6	ENSP00000412253.2	A0A0C4DG78

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.0000377

AC:

AN:

212330

AF XY:

0.0000258

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000225

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000107

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000104

AC:

AN:

1438028

Hom.:

Cov.:

AF XY:

0.00000842

AC XY:

AN XY:

713004

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32980

American (AMR)

AF:

0.000262

AC:

AN:

42032

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25086

East Asian (EAS)

AF:

0.00

AC:

AN:

38992

South Asian (SAS)

AF:

0.00

AC:

AN:

83270

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

9.09e-7

AC:

AN:

1100428

Other (OTH)

AF:

0.0000506

AC:

AN:

59240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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

AF:

0.0000263

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41454

American (AMR)

AF:

0.000262

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.0000167

AC:

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

0.13

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.028

Eigen

Benign

-0.86

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.53

M_CAP

Benign

0.0057

MetaRNN

Benign

0.058

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.81

PhyloP100

0.0

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.83

REVEL

Benign

0.0020

Sift

Benign

0.097

Sift4G

Uncertain

0.045

Polyphen

0.28

Vest4

0.20

MutPred

0.24

Gain of glycosylation at A402 (P = 0.0579)

MVP

0.093

MPC

0.36

ClinPred

0.046

GERP RS

1.1

Varity_R

0.13

gMVP

0.22

Mutation Taster

=96/4

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over