Variant 15-84604310-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_181877.4(ZSCAN2):c.383T>C(p.Leu128Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000806 in 1,612,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ZSCAN2
NM_181877.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.28

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.769

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN2	NM_181877.4 linkuse as main transcript	c.383T>C	p.Leu128Ser	missense_variant	2/3	ENST00000546148.6	NP_870992.2
LOC105370947	XR_932550.1 linkuse as main transcript	n.190-325A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZSCAN2	ENST00000546148.6 linkuse as main transcript	c.383T>C	p.Leu128Ser	missense_variant	2/3	2	NM_181877.4	ENSP00000445451	P1	Q7Z7L9-1
ZSCAN2-AS1	ENST00000618330.3 linkuse as main transcript	n.1548-325A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

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:

0.00

Gnomad OTH

AF:

0.000479

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460096

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726258

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000524

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000479

Bravo

AF:

0.000121

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 27, 2023

The c.383T>C (p.L128S) alteration is located in exon 2 (coding exon 1) of the ZSCAN2 gene. This alteration results from a T to C substitution at nucleotide position 383, causing the leucine (L) at amino acid position 128 to be replaced by a serine (S). 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

Pathogenic

0.72

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.070

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

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

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.89

.;.;D;D;D;D;D;D

M_CAP

Benign

0.029

MetaRNN

Pathogenic

0.77

D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.96

MutationAssessor

Pathogenic

3.8

H;H;H;H;.;.;.;.

MutationTaster

Benign

0.98

D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.6

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

REVEL

Uncertain

0.33

Sift

Uncertain

0.0020

D;D;D;D;D;D;D;D

Sift4G

Benign

0.12

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

Polyphen

1.0

D;D;D;D;.;D;D;D

Vest4

0.80

MutPred

0.69

Gain of glycosylation at L128 (P = 0.0084);Gain of glycosylation at L128 (P = 0.0084);Gain of glycosylation at L128 (P = 0.0084);Gain of glycosylation at L128 (P = 0.0084);Gain of glycosylation at L128 (P = 0.0084);Gain of glycosylation at L128 (P = 0.0084);Gain of glycosylation at L128 (P = 0.0084);Gain of glycosylation at L128 (P = 0.0084);

MVP

0.46

MPC

0.52

ClinPred

0.99

GERP RS

5.6

Varity_R

0.25

gMVP

0.42

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

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