rs2298566

Variant names:

• chr11-130880747-A-C
• rs2298566
• NM_014758.3:c.2633T>G

Your query was ambiguous. Multiple possible variants found:

• chr11-130880747-A-C
• chr11-130880747-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206

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]

ACMG classification

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	c.2633T>G	p.Leu878Arg	missense_variant	Exon 9 of 11	ENST00000265909.9	NP_055573.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNX19	ENST00000265909.9	c.2633T>G	p.Leu878Arg	missense_variant	Exon 9 of 11	1	NM_014758.3	ENSP00000265909.4

Frequencies

GnomAD3 genomes AF: 0.797 AC: 121140 AN: 151990 Hom.: 48886 Cov.: 32

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

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.: 48 AF XY: 0.753 AC XY: 545364 AN XY: 723966

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.: 32 AF XY: 0.797 AC XY: 59264 AN XY: 74332

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	T
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	N
LIST_S2	Benign	0.030	T;T;T;.;T
MetaRNN	Benign	0.0000027	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.7	N;.;.;.;.
PrimateAI	Benign	0.23	T
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	T
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

Other links and lift over

dbSNP: rs2298566; hg19: chr11-130750642; COSMIC: COSV56283815;