Genetic Variant ZSCAN4:p.Leu150Phe (chr19-57677967-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152677.4(ZSCAN4):c.450A>T(p.Leu150Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,324 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZSCAN4
NM_152677.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.160

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.065487266).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152677.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSCAN4	NM_152677.4	MANE Select	c.450A>T	p.Leu150Phe	missense	Exon 4 of 5	NP_689890.1	Q8NAM6
	ZSCAN4	NM_001384833.1		c.450A>T	p.Leu150Phe	missense	Exon 6 of 7	NP_001371762.1	Q8NAM6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSCAN4	ENST00000318203.9	TSL:2 MANE Select	c.450A>T	p.Leu150Phe	missense	Exon 4 of 5	ENSP00000321963.4	Q8NAM6

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000430

AC:

AN:

232796

AF XY:

0.00000796

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000933

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1443384

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717434

African (AFR)

AF:

0.00

AC:

AN:

32532

American (AMR)

AF:

0.00

AC:

AN:

40302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24872

East Asian (EAS)

AF:

0.00

AC:

AN:

39644

South Asian (SAS)

AF:

0.00

AC:

AN:

82250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52974

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5676

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105506

Other (OTH)

AF:

0.00

AC:

AN:

59628

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41568

American (AMR)

AF:

0.00

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.058

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.63

M_CAP

Benign

0.0047

MetaRNN

Benign

0.065

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

PhyloP100

0.16

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.0

REVEL

Benign

0.061

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.021

Polyphen

0.81

Vest4

0.29

MutPred

0.29

Gain of sheet (P = 0.1208)

MVP

0.048

MPC

0.47

ClinPred

0.24

GERP RS

-0.088

Varity_R

0.11

gMVP

0.039

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over