Variant chr6-28434839-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001012455.2(ZSCAN23):c.796G>A(p.Glu266Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000227 in 1,587,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

ZSCAN23
NM_001012455.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.43

Variant links:

Genes affected

ZSCAN23 (HGNC:21193): (zinc finger and SCAN domain containing 23) Enables sequence-specific double-stranded 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]

ZSCAN23 links:

ZSCAN23 (HGNC:):

ZSCAN23 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=0.06495729).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN23	NM_001012455.2 linkuse as main transcript	c.796G>A	p.Glu266Lys	missense_variant	4/4	ENST00000289788.5	NP_001012458.1	Q3MJ62

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZSCAN23	ENST00000289788.5 linkuse as main transcript	c.796G>A	p.Glu266Lys	missense_variant	4/4	1	NM_001012455.2	ENSP00000289788.4	Q3MJ62
ZSCAN23	ENST00000481983.5 linkuse as main transcript	n.*207G>A		non_coding_transcript_exon_variant	3/4	5		ENSP00000435430.1	G3V1D5
ZSCAN23	ENST00000481983.5 linkuse as main transcript	n.*207G>A		3_prime_UTR_variant	3/4	5		ENSP00000435430.1	G3V1D5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000145

AC:

AN:

207198

Hom.:

AF XY:

0.00

AC XY:

AN XY:

111118

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000689

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:

0.0000110

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000223

AC:

AN:

1435860

Hom.:

Cov.:

AF XY:

0.0000197

AC XY:

AN XY:

711732

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000501

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:

0.0000264

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152076

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000665

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2023

The c.796G>A (p.E266K) alteration is located in exon 4 (coding exon 3) of the ZSCAN23 gene. This alteration results from a G to A substitution at nucleotide position 796, causing the glutamic acid (E) at amino acid position 266 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.92

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0013

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.26

M_CAP

Benign

0.0039

MetaRNN

Benign

0.065

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.52

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.15

REVEL

Benign

0.070

Sift

Benign

0.081

Sift4G

Benign

0.42

Polyphen

0.30

Vest4

0.23

MutPred

0.47

Gain of methylation at E266 (P = 0.0071);

MVP

0.25

MPC

0.82

ClinPred

0.22

GERP RS

3.6

Varity_R

0.076

gMVP

0.093

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over