dbSNP rs2298566: SNX19:p.Leu878Arg (chr11-130880747-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014758.3(SNX19):c.2633T>G(p.Leu878Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 1,608,974 control chromosomes in the GnomAD database, including 461,553 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.80 ( 48931 hom., cov: 32)

Exomes 𝑓: 0.75 ( 412622 hom. )

Consequence

SNX19
NM_014758.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.206

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.6984112E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX19	NM_014758.3 link	c.2633T>G	p.Leu878Arg	missense_variant	Exon 9 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.2633T>G	p.Leu878Arg	missense_variant	Exon 9 of 11	1	NM_014758.3	ENSP00000265909.4		Q92543-1

Frequencies

GnomAD3 genomes

AF:

0.797

AC:

121140

AN:

151990

Hom.:

48886

Cov.:

show subpopulations

Gnomad AFR

AF:

0.918

Gnomad AMI

AF:

0.714

Gnomad AMR

AF:

0.745

Gnomad ASJ

AF:

0.732

Gnomad EAS

AF:

0.690

Gnomad SAS

AF:

0.837

Gnomad FIN

AF:

0.807

Gnomad MID

AF:

0.759

Gnomad NFE

AF:

0.744

Gnomad OTH

AF:

0.764

GnomAD3 exomes

AF:

0.773

AC:

193604

AN:

250368

Hom.:

75298

AF XY:

0.773

AC XY:

104529

AN XY:

135298

show subpopulations

Gnomad AFR exome

AF:

0.918

Gnomad AMR exome

AF:

0.762

Gnomad ASJ exome

AF:

0.716

Gnomad EAS exome

AF:

0.700

Gnomad SAS exome

AF:

0.838

Gnomad FIN exome

AF:

0.809

Gnomad NFE exome

AF:

0.749

Gnomad OTH exome

AF:

0.762

GnomAD4 exome

AF:

0.751

AC:

1094346

AN:

1456866

Hom.:

412622

Cov.:

AF XY:

0.753

AC XY:

545364

AN XY:

723966

show subpopulations

Gnomad4 AFR exome

AF:

0.921

Gnomad4 AMR exome

AF:

0.761

Gnomad4 ASJ exome

AF:

0.721

Gnomad4 EAS exome

AF:

0.722

Gnomad4 SAS exome

AF:

0.834

Gnomad4 FIN exome

AF:

0.808

Gnomad4 NFE exome

AF:

0.738

Gnomad4 OTH exome

AF:

0.759

GnomAD4 genome

AF:

0.797

AC:

121242

AN:

152108

Hom.:

48931

Cov.:

AF XY:

0.797

AC XY:

59264

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.918

Gnomad4 AMR

AF:

0.745

Gnomad4 ASJ

AF:

0.732

Gnomad4 EAS

AF:

0.690

Gnomad4 SAS

AF:

0.837

Gnomad4 FIN

AF:

0.807

Gnomad4 NFE

AF:

0.744

Gnomad4 OTH

AF:

0.762

Alfa

AF:

0.750

Hom.:

97555

Bravo

AF:

0.795

TwinsUK

AF:

0.740

AC:

2743

ALSPAC

AF:

0.732

AC:

2822

ESP6500AA

AF:

0.919

AC:

4047

ESP6500EA

AF:

0.750

AC:

6442

ExAC

AF:

0.780

AC:

94715

Asia WGS

AF:

0.799

AC:

2779

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.035

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

2.7

DANN

Benign

0.38

DEOGEN2

Benign

0.00068

T;.;.;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0022

LIST_S2

Benign

0.030

T;T;T;.;T

MetaRNN

Benign

0.0000027

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.7

N;.;.;.;.

PrimateAI

Benign

0.23

PROVEAN

Benign

2.8

N;N;N;N;N

REVEL

Benign

0.049

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

B;.;.;.;.

Vest4

0.19

MPC

0.16

ClinPred

0.000012

GERP RS

0.075

Varity_R

0.075

gMVP

0.28

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over