Variant 19-57678455-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_152677.4(ZSCAN4):c.852G>C(p.Glu284Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00418 in 1,614,124 control chromosomes in the GnomAD database, including 238 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.022 ( 133 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 105 hom. )

Consequence

ZSCAN4
NM_152677.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.32

Variant links:

Genes affected

ZSCAN4 (HGNC:23709): (zinc finger and SCAN domain containing 4) The ZSCAN4 gene encodes a protein involved in telomere maintenance and with a key role in the critical feature of mouse embryonic stem (ES) cells, namely, defying cellular senescence and maintaining normal karyotype for many cell divisions in culture (Zalzman et al., 2010 [PubMed 20336070]).[supplied by OMIM, May 2010]

ZSCAN4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027216375).

BP6

Variant 19-57678455-G-C is Benign according to our data. Variant chr19-57678455-G-C is described in ClinVar as [Benign]. Clinvar id is 777511.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ZSCAN4	NM_152677.4 linkuse as main transcript	c.852G>C	p.Glu284Asp	missense_variant	5/5	ENST00000318203.9
ZSCAN4	NM_001384833.1 linkuse as main transcript	c.852G>C	p.Glu284Asp	missense_variant	7/7
ZSCAN4	XM_017026458.1 linkuse as main transcript	c.852G>C	p.Glu284Asp	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZSCAN4	ENST00000318203.9 linkuse as main transcript	c.852G>C	p.Glu284Asp	missense_variant	5/5	2	NM_152677.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0218

AC:

3310

AN:

152130

Hom.:

132

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0757

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00825

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00617

AC:

1550

AN:

251318

Hom.:

AF XY:

0.00452

AC XY:

614

AN XY:

135834

show subpopulations

Gnomad AFR exome

AF:

0.0798

Gnomad AMR exome

AF:

0.00521

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000475

Gnomad OTH exome

AF:

0.00277

GnomAD4 exome

AF:

0.00234

AC:

3426

AN:

1461876

Hom.:

105

Cov.:

AF XY:

0.00205

AC XY:

1491

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0755

Gnomad4 AMR exome

AF:

0.00570

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000312

Gnomad4 OTH exome

AF:

0.00444

GnomAD4 genome

AF:

0.0218

AC:

3323

AN:

152248

Hom.:

133

Cov.:

AF XY:

0.0210

AC XY:

1561

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0758

Gnomad4 AMR

AF:

0.00830

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.0133

Alfa

AF:

0.00382

Hom.:

Bravo

AF:

0.0249

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0747

AC:

329

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00745

AC:

905

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.83

Cadd

Benign

8.3

Dann

Benign

0.95

DEOGEN2

Benign

0.014

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.056

MetaRNN

Benign

0.0027

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.3

L;L

MutationTaster

Benign

1.0

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.55

N;.

REVEL

Benign

0.031

Sift

Benign

0.44

T;.

Sift4G

Benign

0.41

T;T

Polyphen

0.053

B;B

Vest4

0.088

MutPred

0.18

Gain of glycosylation at S285 (P = 0.1185);Gain of glycosylation at S285 (P = 0.1185);

MVP

0.092

MPC

0.092

ClinPred

0.0036

GERP RS

1.6

Varity_R

0.031

gMVP

0.089

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