Genetic Variant ZSCAN2:p.Pro57Ser (chr15-84604096-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_181877.4(ZSCAN2):c.169C>T(p.Pro57Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

ZSCAN2
NM_181877.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.232

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.060049057).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN2	NM_181877.4 link	c.169C>T	p.Pro57Ser	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.169C>T	p.Pro57Ser	missense_variant	Exon 2 of 3	2	NM_181877.4	ENSP00000445451.1		Q7Z7L9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461848

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

6.4

DANN

Benign

0.72

DEOGEN2

Benign

0.026

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

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.79

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

M_CAP

Benign

0.0054

MetaRNN

Benign

0.060

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

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.34

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

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.46

N;N;N;N;N;N;N;N;N

REVEL

Benign

0.045

Sift

Benign

0.21

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

Sift4G

Benign

0.35

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

Polyphen

0.0, 0.0080, 0.0020, 0.023, 0.019

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

Vest4

0.22, 0.22, 0.17, 0.18, 0.22, 0.20, 0.20, 0.20

MutPred

0.42

Gain of phosphorylation at P57 (P = 0.0132);Gain of phosphorylation at P57 (P = 0.0132);Gain of phosphorylation at P57 (P = 0.0132);Gain of phosphorylation at P57 (P = 0.0132);Gain of phosphorylation at P57 (P = 0.0132);Gain of phosphorylation at P57 (P = 0.0132);Gain of phosphorylation at P57 (P = 0.0132);Gain of phosphorylation at P57 (P = 0.0132);Gain of phosphorylation at P57 (P = 0.0132);

MVP

0.10

MPC

0.079

ClinPred

0.076

GERP RS

0.094

Varity_R

0.042

gMVP

0.22

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over