Variant 6-28434895-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.740G>A(p.Arg247Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000521 in 1,554,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.000055 ( 0 hom. )

Consequence

ZSCAN23
NM_001012455.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.467

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=0.05551988).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN23	NM_001012455.2 linkuse as main transcript	c.740G>A	p.Arg247Lys	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.740G>A	p.Arg247Lys	missense_variant	4/4	1	NM_001012455.2	ENSP00000289788.4	Q3MJ62
ZSCAN23	ENST00000481983.5 linkuse as main transcript	n.*151G>A		non_coding_transcript_exon_variant	3/4	5		ENSP00000435430.1	G3V1D5
ZSCAN23	ENST00000486481.1 linkuse as main transcript	n.436G>A		non_coding_transcript_exon_variant	3/3	2
ZSCAN23	ENST00000481983.5 linkuse as main transcript	n.*151G>A		3_prime_UTR_variant	3/4	5		ENSP00000435430.1	G3V1D5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000371

AC:

AN:

161828

Hom.:

AF XY:

0.0000352

AC XY:

AN XY:

85130

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000401

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:

0.0000626

Gnomad OTH exome

AF:

0.000218

GnomAD4 exome

AF:

0.0000549

AC:

AN:

1401902

Hom.:

Cov.:

AF XY:

0.0000535

AC XY:

AN XY:

691620

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000559

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:

0.0000602

Gnomad4 OTH exome

AF:

0.000172

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000199

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

Jun 21, 2022

The c.740G>A (p.R247K) 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 740, causing the arginine (R) at amino acid position 247 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

Benign

0.16

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.021

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.10

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.75

M_CAP

Benign

0.0025

MetaRNN

Benign

0.056

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.62

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.81

REVEL

Benign

0.051

Sift

Benign

0.24

Sift4G

Benign

0.59

Polyphen

0.13

Vest4

0.12

MutPred

0.35

Gain of methylation at R247 (P = 0.0044);

MVP

0.35

MPC

0.31

ClinPred

0.058

GERP RS

3.7

Varity_R

0.17

gMVP

0.14

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