Variant 6-28434560-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001012455.2(ZSCAN23):c.1075A>G(p.Arg359Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000121 in 1,402,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ZSCAN23
NM_001012455.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.87

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37477958).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN23	NM_001012455.2 linkuse as main transcript	c.1075A>G	p.Arg359Gly	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.1075A>G	p.Arg359Gly	missense_variant	4/4	1	NM_001012455.2	ENSP00000289788.4	Q3MJ62
ZSCAN23	ENST00000481983.5 linkuse as main transcript	n.*486A>G		non_coding_transcript_exon_variant	3/4	5		ENSP00000435430.1	G3V1D5
ZSCAN23	ENST00000481983.5 linkuse as main transcript	n.*486A>G		3_prime_UTR_variant	3/4	5		ENSP00000435430.1	G3V1D5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000607

AC:

AN:

164716

Hom.:

AF XY:

0.0000116

AC XY:

AN XY:

86514

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000152

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000121

AC:

AN:

1402032

Hom.:

Cov.:

AF XY:

0.0000101

AC XY:

AN XY:

691694

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000157

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

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 18, 2024

The c.1075A>G (p.R359G) alteration is located in exon 4 (coding exon 3) of the ZSCAN23 gene. This alteration results from a A to G substitution at nucleotide position 1075, causing the arginine (R) at amino acid position 359 to be replaced by a glycine (G). 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

0.97

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.28

M_CAP

Benign

0.0062

MetaRNN

Benign

0.37

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

PrimateAI

Uncertain

0.65

PROVEAN

Pathogenic

-5.1

REVEL

Benign

0.16

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.33

MutPred

0.51

Loss of phosphorylation at T356 (P = 0.1003);

MVP

0.48

MPC

1.0

ClinPred

0.97

GERP RS

3.9

Varity_R

0.56

gMVP

0.13

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