Variant 16-3089878-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_032805.3(ZSCAN10):c.1556G>A(p.Arg519Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000219 in 1,536,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

ZSCAN10
NM_032805.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.11

Variant links:

Genes affected

ZSCAN10 (HGNC:12997): (zinc finger and SCAN domain containing 10) 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 negative regulation of transcription, DNA-templated and regulation of transcription by RNA polymerase II. Predicted to be located in nucleoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZSCAN10 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=0.032866836).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN10	NM_032805.3 linkuse as main transcript	c.1556G>A	p.Arg519Gln	missense_variant	6/6	ENST00000576985.6	NP_116194.2	Q96SZ4I3L1J3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZSCAN10	ENST00000576985.6 linkuse as main transcript	c.1556G>A	p.Arg519Gln	missense_variant	6/6	5	NM_032805.3	ENSP00000458879.2	I3L1J3
ZSCAN10	ENST00000252463.6 linkuse as main transcript	c.1391G>A	p.Arg464Gln	missense_variant	5/5	1		ENSP00000252463.2	Q96SZ4-1
ZSCAN10	ENST00000538082.5 linkuse as main transcript	c.1145G>A	p.Arg382Gln	missense_variant	5/5	4		ENSP00000440047.2	Q96SZ4-3
ZSCAN10	ENST00000575108.5 linkuse as main transcript	c.374G>A	p.Arg125Gln	missense_variant	5/5	2		ENSP00000459520.1	Q96SZ4-2

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.000206

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000596

AC:

AN:

134140

Hom.:

AF XY:

0.0000272

AC XY:

AN XY:

73516

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:

0.0000435

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000138

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000228

AC:

315

AN:

1384430

Hom.:

Cov.:

AF XY:

0.000227

AC XY:

155

AN XY:

683420

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000561

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:

0.000273

Gnomad4 OTH exome

AF:

0.000329

GnomAD4 genome

AF:

0.000144

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000117

Hom.:

Bravo

AF:

0.000174

ExAC

AF:

0.0000390

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3476

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

May 17, 2023

The c.1391G>A (p.R464Q) alteration is located in exon 5 (coding exon 5) of the ZSCAN10 gene. This alteration results from a G to A substitution at nucleotide position 1391, causing the arginine (R) at amino acid position 464 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

Benign

0.10

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.71

CADD

Benign

7.6

DANN

Benign

0.95

DEOGEN2

Benign

0.0035

T;T;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.31

T;T;T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.033

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.025

.;N;.;.

PrimateAI

Benign

0.47

PROVEAN

Benign

0.050

.;N;.;N

REVEL

Benign

0.031

Sift

Benign

0.18

.;T;.;T

Sift4G

Benign

0.81

T;T;T;T

Polyphen

0.089, 0.043

.;B;B;.

Vest4

0.076

MVP

0.20

MPC

0.91

ClinPred

0.048

GERP RS

-5.2

Varity_R

0.024

gMVP

0.097

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