Variant 7-29926613-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014766.5(SCRN1):c.925A>G(p.Ile309Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 1,613,958 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 7 hom. )

Consequence

SCRN1
NM_014766.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.39

Variant links:

Genes affected

SCRN1 (HGNC:22192): (secernin 1) This gene likely encodes a member of the secernin family of proteins. A similar protein in rat functions in regulation of exocytosis in mast cells. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2009]

SCRN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017178923).

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCRN1	NM_014766.5 linkuse as main transcript	c.925A>G	p.Ile309Val	missense_variant	7/8	ENST00000242059.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCRN1	ENST00000242059.10 linkuse as main transcript	c.925A>G	p.Ile309Val	missense_variant	7/8	1	NM_014766.5	P1	Q12765-1

Frequencies

GnomAD3 genomes

AF:

0.00125

AC:

190

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000387

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00194

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00117

AC:

293

AN:

251398

Hom.:

AF XY:

0.00112

AC XY:

152

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000323

Gnomad NFE exome

AF:

0.00179

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.00167

AC:

2438

AN:

1461780

Hom.:

Cov.:

AF XY:

0.00163

AC XY:

1186

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.00143

Gnomad4 ASJ exome

AF:

0.00203

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000412

Gnomad4 NFE exome

AF:

0.00198

Gnomad4 OTH exome

AF:

0.00146

GnomAD4 genome

AF:

0.00125

AC:

190

AN:

152178

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00194

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00176

Hom.:

Bravo

AF:

0.00131

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.00121

AC:

147

EpiCase

AF:

0.00196

EpiControl

AF:

0.00166

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

May 27, 2022

The c.985A>G (p.I329V) alteration is located in exon 7 (coding exon 7) of the SCRN1 gene. This alteration results from a A to G substitution at nucleotide position 985, causing the isoleucine (I) at amino acid position 329 to be replaced by a valine (V). 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

0.10

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0042

T;T;.;T;.

Eigen

Benign

0.0046

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.91

M_CAP

Benign

0.0074

MetaRNN

Benign

0.017

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.70

N;N;.;N;.

MutationTaster

Benign

0.90

D;D;D;D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.55

N;N;N;N;N

REVEL

Benign

0.071

Sift

Benign

0.15

T;T;T;T;T

Sift4G

Benign

0.26

T;T;T;T;T

Polyphen

0.0030

B;B;.;B;.

Vest4

0.12

MVP

0.048

MPC

0.20

ClinPred

0.019

GERP RS

5.7

Varity_R

0.075

gMVP

0.57

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