Variant chr2-174399929-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001412209.1(SCRN3):c.-74A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000579 in 1,485,012 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

SCRN3
NM_001412209.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.26

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCRN3	NM_024583.5 linkuse as main transcript	c.167A>G	p.Tyr56Cys	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.167A>G	p.Tyr56Cys	missense_variant	3/8	1	NM_024583.5	ENSP00000272732.6		Q0VDG4-1

Frequencies

GnomAD3 genomes

AF:

0.000134

AC:

AN:

141404

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000300

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00151

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000118

AC:

AN:

169956

Hom.:

AF XY:

0.000138

AC XY:

AN XY:

94340

show subpopulations

Gnomad AFR exome

AF:

0.000373

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000855

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000499

AC:

AN:

1343536

Hom.:

Cov.:

AF XY:

0.0000661

AC XY:

AN XY:

665460

show subpopulations

Gnomad4 AFR exome

AF:

0.000337

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000805

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.42e-7

Gnomad4 OTH exome

AF:

0.0000543

GnomAD4 genome

AF:

0.000134

AC:

AN:

141476

Hom.:

Cov.:

AF XY:

0.000147

AC XY:

AN XY:

68088

show subpopulations

Gnomad4 AFR

AF:

0.000299

Gnomad4 AMR

AF:

0.0000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00152

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000988

AC:

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

Feb 07, 2023

The c.167A>G (p.Y56C) alteration is located in exon 3 (coding exon 2) of the SCRN3 gene. This alteration results from a A to G substitution at nucleotide position 167, causing the tyrosine (Y) at amino acid position 56 to be replaced by a cysteine (C). 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

0.28

BayesDel_addAF

Uncertain

0.049

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.42

T;.;T;T;.;T

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

1.0

D;D;D;D;D;D

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.56

D;D;D;D;D;D

MetaSVM

Uncertain

-0.19

MutationAssessor

Pathogenic

3.7

.;.;H;.;.;.

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-8.8

D;D;D;D;D;D

REVEL

Pathogenic

0.72

Sift

Pathogenic

0.0

D;D;D;D;D;D

Sift4G

Uncertain

0.0030

D;D;D;D;D;D

Polyphen

1.0

.;.;D;.;.;.

Vest4

0.90, 0.91

MVP

0.43

MPC

0.25

ClinPred

0.70

GERP RS

5.6

Varity_R

0.87

gMVP

0.87

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