Variant 16-3089624-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032805.3(ZSCAN10):c.1810C>T(p.Arg604Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000419 in 1,432,830 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: 33)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

ZSCAN10
NM_032805.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.437

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 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=0.33872265).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN10	NM_032805.3 linkuse as main transcript	c.1810C>T	p.Arg604Trp	missense_variant	6/6	ENST00000576985.6	NP_116194.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZSCAN10	ENST00000576985.6 linkuse as main transcript	c.1810C>T	p.Arg604Trp	missense_variant	6/6	5	NM_032805.3	ENSP00000458879	P1
ZSCAN10	ENST00000252463.6 linkuse as main transcript	c.1645C>T	p.Arg549Trp	missense_variant	5/5	1		ENSP00000252463		Q96SZ4-1
ZSCAN10	ENST00000538082.5 linkuse as main transcript	c.1399C>T	p.Arg467Trp	missense_variant	5/5	4		ENSP00000440047		Q96SZ4-3
ZSCAN10	ENST00000575108.5 linkuse as main transcript	c.628C>T	p.Arg210Trp	missense_variant	5/5	2		ENSP00000459520		Q96SZ4-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000148

AC:

AN:

202288

Hom.:

AF XY:

0.0000270

AC XY:

AN XY:

111092

show subpopulations

Gnomad AFR exome

AF:

0.0000816

Gnomad AMR exome

AF:

0.0000332

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:

0.0000115

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000419

AC:

AN:

1432830

Hom.:

Cov.:

AF XY:

0.00000563

AC XY:

AN XY:

710332

show subpopulations

Gnomad4 AFR exome

AF:

0.0000919

Gnomad4 AMR exome

AF:

0.0000243

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:

0.00000182

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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 16, 2023

The c.1645C>T (p.R549W) alteration is located in exon 5 (coding exon 5) of the ZSCAN10 gene. This alteration results from a C to T substitution at nucleotide position 1645, causing the arginine (R) at amino acid position 549 to be replaced by a tryptophan (W). 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

0.50

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;T;.;.

Eigen

Uncertain

0.30

Eigen_PC

Benign

0.15

FATHMM_MKL

Benign

0.32

LIST_S2

Uncertain

0.93

D;D;D;D

M_CAP

Benign

0.055

MetaRNN

Benign

0.34

T;T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Pathogenic

3.0

.;M;.;.

MutationTaster

Benign

0.71

N;N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Pathogenic

-5.4

.;D;.;D

REVEL

Benign

0.19

Sift

Uncertain

0.0010

.;D;.;D

Sift4G

Pathogenic

0.0010

D;D;D;D

Polyphen

1.0

.;D;D;.

Vest4

0.69

MutPred

0.46

.;Loss of disorder (P = 0.0132);.;.;

MVP

0.60

MPC

1.9

ClinPred

0.94

GERP RS

3.1

Varity_R

0.46

gMVP

0.39

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