Genetic Variant ZSCAN18:p.Ala402Thr (chr19-58085014-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001145543.2(ZSCAN18):c.1204G>A(p.Ala402Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000503 in 1,590,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. A402P) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

ZSCAN18
NM_001145543.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.010904908).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN18	NM_001145543.2 link	c.1204G>A	p.Ala402Thr	missense_variant	Exon 7 of 7	ENST00000601144.6	NP_001139015.1	Q8TBC5-1A0A024R4T0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSCAN18	ENST00000601144.6 link	c.1204G>A	p.Ala402Thr	missense_variant	Exon 7 of 7	1	NM_001145543.2	ENSP00000468934.1		Q8TBC5-1

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000706

AC:

AN:

212330

Hom.:

AF XY:

0.0000602

AC XY:

AN XY:

116308

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.0000321

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000243

AC:

AN:

1438028

Hom.:

Cov.:

AF XY:

0.0000238

AC XY:

AN XY:

713004

show subpopulations

Gnomad4 AFR exome

AF:

0.000819

Gnomad4 AMR exome

AF:

0.0000714

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000675

GnomAD4 genome

AF:

0.000295

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00103

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000980

Hom.:

Bravo

AF:

0.000344

ESP6500AA

AF:

0.00137

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000100

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.77

CADD

Benign

8.7

DANN

Benign

0.91

DEOGEN2

Benign

0.0067

T;T;T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.56

T;.;T;T;T

M_CAP

Benign

0.0039

MetaRNN

Benign

0.011

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.46

.;N;N;.;.

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.21

.;N;.;N;.

REVEL

Benign

0.016

Sift

Benign

0.16

.;T;.;T;.

Sift4G

Benign

0.49

T;T;T;T;T

Polyphen

0.064

.;B;B;.;.

Vest4

0.028, 0.081, 0.10, 0.11

MVP

0.17

MPC

0.068

ClinPred

0.0070

GERP RS

1.1

Varity_R

0.046

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over