Genetic Variant ZSCAN2:p.Leu16Phe (chr15-84603975-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_181877.4(ZSCAN2):c.48G>C(p.Leu16Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

ZSCAN2
NM_181877.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.04

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07940808).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN2	NM_181877.4 link	c.48G>C	p.Leu16Phe	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.48G>C	p.Leu16Phe	missense_variant	Exon 2 of 3	2	NM_181877.4	ENSP00000445451.1		Q7Z7L9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250348

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135626

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461764

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727196

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:

0.00000809

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 15, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.48G>C (p.L16F) alteration is located in exon 2 (coding exon 1) of the ZSCAN2 gene. This alteration results from a G to C substitution at nucleotide position 48, causing the leucine (L) at amino acid position 16 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.047

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

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.12

LIST_S2

Uncertain

0.87

D;.;D;.;D;D;T;D;T;D;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.079

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

.;L;.;L;.;L;.;L;.;.;.;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.5

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

REVEL

Benign

0.053

Sift

Uncertain

0.0090

D;T;D;T;.;T;.;T;D;T;D;T

Sift4G

Benign

0.065

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

Polyphen

0.12, 0.88, 0.74, 0.93, 0.96, 0.34

.;B;.;B;.;P;.;P;.;P;D;B

Vest4

0.37, 0.35, 0.35, 0.37, 0.42, 0.41, 0.40

MutPred

0.20

Loss of loop (P = 0.1258);Loss of loop (P = 0.1258);Loss of loop (P = 0.1258);Loss of loop (P = 0.1258);Loss of loop (P = 0.1258);Loss of loop (P = 0.1258);Loss of loop (P = 0.1258);Loss of loop (P = 0.1258);Loss of loop (P = 0.1258);Loss of loop (P = 0.1258);Loss of loop (P = 0.1258);Loss of loop (P = 0.1258);

MVP

0.17

MPC

0.10

ClinPred

0.21

GERP RS

1.3

Varity_R

0.058

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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