Variant 11-130903384-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_014758.3(SNX19):c.2444G>C(p.Gly815Ala) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00866 in 1,611,990 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/25 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0088 ( 80 hom. )

Consequence

SNX19
NM_014758.3 missense, splice_region

Scores

Splicing: ADA: 0.9589

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.830

Variant links:

Genes affected

SNX19 (HGNC:21532): (sorting nexin 19) Islet antigen-2 (IA-2) is an autoantigen in type 1 diabetes and plays a role in insulin secretion. IA-2 is found in dense-core secretory vesicles and interacts with the product of this gene, a sorting nexin. In mouse pancreatic beta-cells, the encoded protein influenced insulin secretion by stabilizing the number of dense-core secretory vesicles. [provided by RefSeq, Dec 2016]

SNX19 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP6

Variant 11-130903384-C-G is Benign according to our data. Variant chr11-130903384-C-G is described in ClinVar as [Benign]. Clinvar id is 786927.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX19	NM_014758.3 link	c.2444G>C	p.Gly815Ala	missense_variant, splice_region_variant	Exon 8 of 11	ENST00000265909.9	NP_055573.3	Q92543-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNX19	ENST00000265909.9 link	c.2444G>C	p.Gly815Ala	missense_variant, splice_region_variant	Exon 8 of 11	1	NM_014758.3	ENSP00000265909.4		Q92543-1

Frequencies

GnomAD3 genomes

AF:

0.00688

AC:

1047

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00949

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00669

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0104

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.00688

AC:

1724

AN:

250642

Hom.:

AF XY:

0.00671

AC XY:

909

AN XY:

135454

show subpopulations

Gnomad AFR exome

AF:

0.000924

Gnomad AMR exome

AF:

0.00619

Gnomad ASJ exome

AF:

0.00417

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00128

Gnomad FIN exome

AF:

0.00741

Gnomad NFE exome

AF:

0.0106

Gnomad OTH exome

AF:

0.00820

GnomAD4 exome

AF:

0.00884

AC:

12907

AN:

1459740

Hom.:

Cov.:

AF XY:

0.00866

AC XY:

6288

AN XY:

726214

show subpopulations

Gnomad4 AFR exome

AF:

0.00120

Gnomad4 AMR exome

AF:

0.00609

Gnomad4 ASJ exome

AF:

0.00375

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00105

Gnomad4 FIN exome

AF:

0.00820

Gnomad4 NFE exome

AF:

0.0103

Gnomad4 OTH exome

AF:

0.00814

GnomAD4 genome

AF:

0.00688

AC:

1047

AN:

152250

Hom.:

Cov.:

AF XY:

0.00615

AC XY:

458

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00200

Gnomad4 AMR

AF:

0.00948

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00669

Gnomad4 NFE

AF:

0.0104

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.00814

Hom.:

Bravo

AF:

0.00700

TwinsUK

AF:

0.0116

AC:

ALSPAC

AF:

0.0101

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00966

AC:

ExAC

AF:

0.00662

AC:

804

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0108

EpiControl

AF:

0.0121

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0052

T;.;.;.

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.73

T;T;.;T

M_CAP

Benign

0.0059

MetaRNN

Benign

0.0054

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.;.;.

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.75

N;N;N;N

REVEL

Benign

0.029

Sift

Benign

0.29

T;T;T;T

Sift4G

Benign

0.27

T;T;T;T

Polyphen

0.0070

B;.;.;.

Vest4

0.24

MVP

0.36

MPC

0.12

ClinPred

0.0015

GERP RS

3.5

Varity_R

0.036

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.96

dbscSNV1_RF

Pathogenic

0.81

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.22

Position offset: 0

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