Genetic Variant ZSCAN10:p.Ala749Ser (chr16-3089189-C-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_032805.3(ZSCAN10):c.2245G>T(p.Ala749Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00525 in 1,577,130 control chromosomes in the GnomAD database, including 25 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0054 ( 23 hom. )

Consequence

ZSCAN10
NM_032805.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.06

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0061773956).

BP6

Variant 16-3089189-C-A is Benign according to our data. Variant chr16-3089189-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2646100.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN10	NM_032805.3 link	c.2245G>T	p.Ala749Ser	missense_variant	Exon 6 of 6	ENST00000576985.6	NP_116194.2	Q96SZ4I3L1J3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZSCAN10	ENST00000576985.6 link	c.2245G>T	p.Ala749Ser	missense_variant	Exon 6 of 6	5	NM_032805.3	ENSP00000458879.2	I3L1J3
ZSCAN10	ENST00000252463.6 link	c.2080G>T	p.Ala694Ser	missense_variant	Exon 5 of 5	1		ENSP00000252463.2	Q96SZ4-1
ZSCAN10	ENST00000538082.5 link	c.1834G>T	p.Ala612Ser	missense_variant	Exon 5 of 5	4		ENSP00000440047.2	Q96SZ4-3
ZSCAN10	ENST00000575108.5 link	c.1063G>T	p.Ala355Ser	missense_variant	Exon 5 of 5	2		ENSP00000459520.1	Q96SZ4-2

Frequencies

GnomAD3 genomes

AF:

0.00354

AC:

539

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00497

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00559

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00372

AC:

724

AN:

194582

Hom.:

AF XY:

0.00363

AC XY:

391

AN XY:

107684

show subpopulations

Gnomad AFR exome

AF:

0.000730

Gnomad AMR exome

AF:

0.00470

Gnomad ASJ exome

AF:

0.00375

Gnomad EAS exome

AF:

0.00127

Gnomad SAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.00202

Gnomad NFE exome

AF:

0.00552

Gnomad OTH exome

AF:

0.00240

GnomAD4 exome

AF:

0.00544

AC:

7744

AN:

1424794

Hom.:

Cov.:

AF XY:

0.00526

AC XY:

3725

AN XY:

707908

show subpopulations

Gnomad4 AFR exome

AF:

0.000676

Gnomad4 AMR exome

AF:

0.00541

Gnomad4 ASJ exome

AF:

0.00429

Gnomad4 EAS exome

AF:

0.00131

Gnomad4 SAS exome

AF:

0.000293

Gnomad4 FIN exome

AF:

0.00218

Gnomad4 NFE exome

AF:

0.00626

Gnomad4 OTH exome

AF:

0.00557

GnomAD4 genome

AF:

0.00354

AC:

539

AN:

152336

Hom.:

Cov.:

AF XY:

0.00310

AC XY:

231

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.00497

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00559

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00388

Hom.:

Bravo

AF:

0.00391

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.000691

AC:

ESP6500EA

AF:

0.00564

AC:

ExAC

AF:

0.00333

AC:

399

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ZSCAN10: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0055

T;T;.;.

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.67

T;T;T;T

M_CAP

Benign

0.0095

MetaRNN

Benign

0.0062

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.77

.;N;.;.

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-0.050

.;N;.;.

REVEL

Benign

0.13

Sift

Benign

0.25

.;T;.;.

Sift4G

Benign

0.18

T;T;D;T

Polyphen

0.66, 0.99

.;P;D;.

Vest4

0.34

MVP

0.45

MPC

1.6

ClinPred

0.026

GERP RS

4.0

Varity_R

0.068

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