Genetic Variant ZSCAN2:p.Ile6Ser (chr15-84603944-T-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_181877.4(ZSCAN2):c.17T>G(p.Ile6Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,613,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

ZSCAN2
NM_181877.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0870

Publications

0 publications found

Variant links:

Genes affected

ZSCAN2 (HGNC:20994): (zinc finger and SCAN domain containing 2) The protein encoded by this gene contains several copies of zinc finger motif, which is commonly found in transcriptional regulatory proteins. Studies in mice show that this gene is expressed during embryonic development, and specifically in the testis in adult mice, suggesting that it may play a role in regulating genes in germ cells. Alternative splicing of this gene results in several transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ZSCAN2 links:

ZSCAN2-AS1 (HGNC:56673): (ZSCAN2 antisense RNA 1)

ZSCAN2-AS1 links:

LOC105370947 (HGNC:):

LOC105370947 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009220064).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_181877.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZSCAN2	NM_181877.4	MANE Select	c.17T>G	p.Ile6Ser	missense	Exon 2 of 3	NP_870992.2	Q7Z7L9-1
ZSCAN2	NM_017894.6		c.17T>G	p.Ile6Ser	missense	Exon 2 of 3	NP_060364.4
ZSCAN2	NM_001007072.2		c.17T>G	p.Ile6Ser	missense	Exon 2 of 3	NP_001007073.1	Q7Z7L9-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZSCAN2	ENST00000546148.6	TSL:2 MANE Select	c.17T>G	p.Ile6Ser	missense	Exon 2 of 3	ENSP00000445451.1	Q7Z7L9-1
ZSCAN2	ENST00000327179.6	TSL:1	c.17T>G	p.Ile6Ser	missense	Exon 2 of 3	ENSP00000325123.6	A0A0C4DFQ3
ZSCAN2	ENST00000538076.5	TSL:1	c.17T>G	p.Ile6Ser	missense	Exon 1 of 4	ENSP00000439132.1	F5H3F3

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000523

AC:

AN:

248704

AF XY:

0.0000370

show subpopulations

Gnomad AFR exome

AF:

0.000445

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000358

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000274

AC:

AN:

1461400

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727012

show subpopulations

African (AFR)

AF:

0.000358

AC:

AN:

33480

American (AMR)

AF:

0.0000447

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26108

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53122

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000171

AC:

AN:

1111878

Other (OTH)

AF:

0.0000497

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000105

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.000361

AC:

AN:

41512

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67996

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000148

Hom.:

Bravo

AF:

0.000140

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

Benign

0.13

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.46

CADD

Benign

9.5

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.029

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.056

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.012

MetaRNN

Benign

0.0092

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.087

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.86

REVEL

Benign

0.031

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.0080

Polyphen

0.0050

Vest4

0.24

MVP

0.085

MPC

0.12

ClinPred

0.017

GERP RS

0.33

PromoterAI

-0.043

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.025

gMVP

0.48

Mutation Taster

=95/5

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over