Genetic Variant SCRN3:p.Glu64Gln (chr2-174399952-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024583.5(SCRN3):c.190G>C(p.Glu64Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000049 in 142,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000049 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SCRN3
NM_024583.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.888

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.091545135).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024583.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCRN3	NM_024583.5	MANE Select	c.190G>C	p.Glu64Gln	missense	Exon 3 of 8	NP_078859.2
SCRN3	NM_001412210.1		c.250G>C	p.Glu84Gln	missense	Exon 3 of 8	NP_001399139.1
SCRN3	NM_001412202.1		c.190G>C	p.Glu64Gln	missense	Exon 3 of 8	NP_001399131.1	Q0VDG4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SCRN3	ENST00000272732.11	TSL:1 MANE Select	c.190G>C	p.Glu64Gln	missense	Exon 3 of 8	ENSP00000272732.6	Q0VDG4-1
SCRN3	ENST00000877601.1		c.190G>C	p.Glu64Gln	missense	Exon 3 of 8	ENSP00000547660.1
SCRN3	ENST00000877602.1		c.190G>C	p.Glu64Gln	missense	Exon 3 of 8	ENSP00000547661.1

Frequencies

GnomAD3 genomes

AF:

0.0000490

AC:

AN:

142732

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000186

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

GnomAD2 exomes

AF:

0.0000158

AC:

AN:

189658

AF XY:

0.0000192

show subpopulations

Gnomad AFR exome

AF:

0.000251

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1360088

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

676304

African (AFR)

AF:

0.00

AC:

AN:

27296

American (AMR)

AF:

0.00

AC:

AN:

27416

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23732

East Asian (EAS)

AF:

0.00

AC:

AN:

34158

South Asian (SAS)

AF:

0.00

AC:

AN:

72798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52002

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5442

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1061346

Other (OTH)

AF:

0.00

AC:

AN:

55898

GnomAD4 genome

AF:

0.0000490

AC:

AN:

142732

Hom.:

Cov.:

AF XY:

0.0000727

AC XY:

AN XY:

68766

show subpopulations

African (AFR)

AF:

0.000186

AC:

AN:

37704

American (AMR)

AF:

0.00

AC:

AN:

13864

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3432

East Asian (EAS)

AF:

0.00

AC:

AN:

4934

South Asian (SAS)

AF:

0.00

AC:

AN:

4546

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8444

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66684

Other (OTH)

AF:

0.00

AC:

AN:

1932

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000169

Hom.:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.012

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.44

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.0034

MetaRNN

Benign

0.092

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.71

PhyloP100

0.89

PrimateAI

Benign

0.34

PROVEAN

Benign

0.040

REVEL

Benign

0.019

Sift

Benign

0.41

Sift4G

Benign

0.34

Polyphen

0.023

Vest4

0.15

MVP

0.41

MPC

0.029

ClinPred

0.096

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.041

gMVP

0.54

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over