Genetic Variant ZSCAN2:p.Ser53Pro (chr15-84604084-T-C) – 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_181877.4(ZSCAN2):c.157T>C(p.Ser53Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S53T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZSCAN2
NM_181877.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.403

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0667516).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN2	NM_181877.4 link	c.157T>C	p.Ser53Pro	missense_variant	Exon 2 of 3	ENST00000546148.6	NP_870992.2	Q7Z7L9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSCAN2	ENST00000546148.6 link	c.157T>C	p.Ser53Pro	missense_variant	Exon 2 of 3	2	NM_181877.4	ENSP00000445451.1		Q7Z7L9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251168

AF XY:

0.00

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:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112008

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.038

.;T;.;T;.;.;.;T;.;T

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.64

T;.;T;.;T;T;T;T;T;T

M_CAP

Benign

0.0019

MetaRNN

Benign

0.047

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.39

.;N;.;N;N;N;.;.;.;.

PhyloP100

-0.40

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.4

N;N;D;N;N;N;N;N;N;N

REVEL

Benign

0.063

Sift

Benign

0.20

T;T;D;T;T;T;T;T;T;T

Sift4G

Benign

0.32

T;T;D;T;T;T;T;T;T;T

Polyphen

0.0, 0.0010, 0.0040, 0.012

.;B;.;B;B;B;.;B;B;B

Vest4

0.27, 0.27, 0.26, 0.24, 0.27, 0.27, 0.29, 0.27

MutPred

0.25

Loss of phosphorylation at S53 (P = 0.0113);Loss of phosphorylation at S53 (P = 0.0113);Loss of phosphorylation at S53 (P = 0.0113);Loss of phosphorylation at S53 (P = 0.0113);Loss of phosphorylation at S53 (P = 0.0113);Loss of phosphorylation at S53 (P = 0.0113);Loss of phosphorylation at S53 (P = 0.0113);Loss of phosphorylation at S53 (P = 0.0113);Loss of phosphorylation at S53 (P = 0.0113);Loss of phosphorylation at S53 (P = 0.0113);

MVP

0.16

MPC

0.099

ClinPred

0.053

GERP RS

-0.086

PromoterAI

-0.0030

Neutral

(source)

Varity_R

0.14

gMVP

0.18

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over