NM_001145543.2:c.1408G>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001145543.2(ZSCAN18):c.1408G>A(p.Ala470Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,435,126 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. 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. A470E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

ZSCAN18
NM_001145543.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.845

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05536881).

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.1408G>A	p.Ala470Thr	missense	Exon 7 of 7	NP_001139015.1	Q8TBC5-1
ZSCAN18	NM_001145542.1		c.1576G>A	p.Ala526Thr	missense	Exon 7 of 7	NP_001139014.1	Q8TBC5-3
ZSCAN18	NM_023926.5		c.1408G>A	p.Ala470Thr	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.1408G>A	p.Ala470Thr	missense	Exon 7 of 7	ENSP00000468934.1	Q8TBC5-1
ZSCAN18	ENST00000240727.10	TSL:1	c.1408G>A	p.Ala470Thr	missense	Exon 7 of 7	ENSP00000240727.5	Q8TBC5-1
ZSCAN18	ENST00000433686.6	TSL:1	c.1099G>A	p.Ala367Thr	missense	Exon 6 of 6	ENSP00000412253.2	A0A0C4DG78

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.97e-7

AC:

AN:

1435126

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

712598

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33164

American (AMR)

AF:

0.00

AC:

AN:

41586

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25622

East Asian (EAS)

AF:

0.00

AC:

AN:

38842

South Asian (SAS)

AF:

0.00

AC:

AN:

83470

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43902

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

9.06e-7

AC:

AN:

1103308

Other (OTH)

AF:

0.00

AC:

AN:

59492

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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:

0.00

Hom.:

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

0.10

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.0

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0090

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.45

M_CAP

Benign

0.0069

MetaRNN

Benign

0.055

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.94

PhyloP100

-0.84

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.32

REVEL

Benign

0.012

Sift

Benign

0.15

Sift4G

Benign

0.21

Polyphen

0.019

Vest4

0.036

MutPred

0.22

Gain of phosphorylation at A470 (P = 0.0522)

MVP

0.12

MPC

0.061

ClinPred

0.037

GERP RS

-2.8

Varity_R

0.047

gMVP

0.15

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over