Variant 2-174404244-T-C 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.683T>C(p.Leu228Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

SCRN3
NM_024583.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.39

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=0.068102).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCRN3	NM_024583.5 linkuse as main transcript	c.683T>C	p.Leu228Pro	missense_variant	5/8	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.683T>C	p.Leu228Pro	missense_variant	5/8	1	NM_024583.5	ENSP00000272732.6		Q0VDG4-1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251290

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461598

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

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:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.000338

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000718

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

Jul 06, 2021

The c.683T>C (p.L228P) alteration is located in exon 5 (coding exon 4) of the SCRN3 gene. This alteration results from a T to C substitution at nucleotide position 683, causing the leucine (L) at amino acid position 228 to be replaced by a proline (P). 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

0.080

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0017

.;T

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.068

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.49

.;N

PrimateAI

Benign

0.40

PROVEAN

Benign

0.82

N;N

REVEL

Benign

0.041

Sift

Benign

0.27

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.0010

.;B

Vest4

0.30

MVP

0.11

MPC

0.038

ClinPred

0.064

GERP RS

3.4

Varity_R

0.092

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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