Variant 2-174399964-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024583.5(SCRN3):c.202G>A(p.Val68Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000105 in 1,559,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000069 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

SCRN3
NM_024583.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.03

Variant links:

Genes affected

SCRN3 (HGNC:30382): (secernin 3) Predicted to enable cysteine-type exopeptidase activity and dipeptidase activity. Predicted to be involved in proteolysis. [provided by Alliance of Genome Resources, Apr 2022]

SCRN3 links:

SCRN3 (HGNC:):

SCRN3 links:

Genome browser will be placed here

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=0.16386732).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCRN3	NM_024583.5 linkuse as main transcript	c.202G>A	p.Val68Ile	missense_variant	3/8	ENST00000272732.11	NP_078859.2	Q0VDG4-1Q0VDG5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCRN3	ENST00000272732.11 linkuse as main transcript	c.202G>A	p.Val68Ile	missense_variant	3/8	1	NM_024583.5	ENSP00000272732.6		Q0VDG4-1

Frequencies

GnomAD3 genomes

AF:

0.0000759

AC:

AN:

144834

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000260

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000200

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000134

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000992

AC:

AN:

211790

Hom.:

AF XY:

0.000129

AC XY:

AN XY:

115836

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000729

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000199

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000108

AC:

153

AN:

1414450

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

703254

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:

0.000134

Gnomad4 OTH exome

AF:

0.000103

GnomAD4 genome

AF:

0.0000690

AC:

AN:

144918

Hom.:

Cov.:

AF XY:

0.0000428

AC XY:

AN XY:

70114

show subpopulations

Gnomad4 AFR

AF:

0.0000259

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000134

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000119

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000140

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Aug 12, 2021

The c.202G>A (p.V68I) alteration is located in exon 3 (coding exon 2) of the SCRN3 gene. This alteration results from a G to A substitution at nucleotide position 202, causing the valine (V) at amino acid position 68 to be replaced by an isoleucine (I). 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

0.078

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.058

T;.;T;T;.;T

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.86

D;T;D;D;D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.16

T;T;T;T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.7

.;.;M;.;.;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.87

N;N;N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.21

T;T;T;T;T;T

Sift4G

Benign

0.21

T;T;T;T;T;T

Polyphen

1.0

.;.;D;.;.;.

Vest4

0.21, 0.15

MVP

0.16

MPC

0.043

ClinPred

0.36

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.44

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