Variant chr6-28434784-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001012455.2(ZSCAN23):c.851G>A(p.Arg284Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000937 in 1,601,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000083 ( 0 hom. )

Consequence

ZSCAN23
NM_001012455.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22907725).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN23	NM_001012455.2 linkuse as main transcript	c.851G>A	p.Arg284Gln	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.851G>A	p.Arg284Gln	missense_variant	4/4	1	NM_001012455.2	ENSP00000289788.4	Q3MJ62
ZSCAN23	ENST00000481983.5 linkuse as main transcript	n.*262G>A		non_coding_transcript_exon_variant	3/4	5		ENSP00000435430.1	G3V1D5
ZSCAN23	ENST00000481983.5 linkuse as main transcript	n.*262G>A		3_prime_UTR_variant	3/4	5		ENSP00000435430.1	G3V1D5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000872

AC:

AN:

229344

Hom.:

AF XY:

0.00000808

AC XY:

AN XY:

123780

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000315

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:

0.00000977

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000828

AC:

AN:

1449398

Hom.:

Cov.:

AF XY:

0.00000834

AC XY:

AN XY:

719746

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.0000236

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:

0.00000633

Gnomad4 OTH exome

AF:

0.0000500

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152108

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

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

Aug 21, 2024

The c.851G>A (p.R284Q) 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 851, causing the arginine (R) at amino acid position 284 to be replaced by a glutamine (Q). 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

Uncertain

0.40

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.038

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.39

M_CAP

Benign

0.0035

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.8

REVEL

Benign

0.11

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.13

MutPred

0.70

Loss of phosphorylation at S287 (P = 0.0798);

MVP

0.34

MPC

0.37

ClinPred

0.68

GERP RS

3.3

Varity_R

0.17

gMVP

0.085

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