Variant 11-130880697-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_014758.3(SNX19):c.2683C>T(p.Arg895Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0071 in 1,612,362 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R895Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0071 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0071 ( 94 hom. )

Consequence

SNX19
NM_014758.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.55

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009041548).

BP6

Variant 11-130880697-G-A is Benign according to our data. Variant chr11-130880697-G-A is described in ClinVar as [Benign]. Clinvar id is 784522.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX19	NM_014758.3 linkuse as main transcript	c.2683C>T	p.Arg895Trp	missense_variant	9/11	ENST00000265909.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX19	ENST00000265909.9 linkuse as main transcript	c.2683C>T	p.Arg895Trp	missense_variant	9/11	1	NM_014758.3	P1	Q92543-1

Frequencies

GnomAD3 genomes

AF:

0.00707

AC:

1076

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.0485

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00667

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00859

AC:

2153

AN:

250582

Hom.:

AF XY:

0.00845

AC XY:

1144

AN XY:

135404

show subpopulations

Gnomad AFR exome

AF:

0.000985

Gnomad AMR exome

AF:

0.00163

Gnomad ASJ exome

AF:

0.00676

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000687

Gnomad FIN exome

AF:

0.0451

Gnomad NFE exome

AF:

0.00858

Gnomad OTH exome

AF:

0.00720

GnomAD4 exome

AF:

0.00711

AC:

10375

AN:

1460062

Hom.:

Cov.:

AF XY:

0.00707

AC XY:

5131

AN XY:

726080

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.00197

Gnomad4 ASJ exome

AF:

0.00820

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000605

Gnomad4 FIN exome

AF:

0.0417

Gnomad4 NFE exome

AF:

0.00667

Gnomad4 OTH exome

AF:

0.00559

GnomAD4 genome

AF:

0.00707

AC:

1076

AN:

152300

Hom.:

Cov.:

AF XY:

0.00873

AC XY:

650

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.0485

Gnomad4 NFE

AF:

0.00667

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00625

Hom.:

Bravo

AF:

0.00380

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00675

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00687

AC:

ExAC

AF:

0.00865

AC:

1050

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00498

EpiControl

AF:

0.00700

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.025

T;.;.;.;.

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.091

FATHMM_MKL

Benign

0.55

LIST_S2

Uncertain

0.93

D;D;D;.;D

MetaRNN

Benign

0.0090

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

M;.;.;.;.

MutationTaster

Benign

0.97

N;N;N;N;N;N;N

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.8

D;D;D;D;D

REVEL

Benign

0.19

Sift

Uncertain

0.0040

D;D;D;D;D

Sift4G

Uncertain

0.0080

D;D;D;D;D

Polyphen

1.0

D;.;.;.;.

Vest4

0.48

MVP

0.45

MPC

0.51

ClinPred

0.024

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.083

gMVP

0.31

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