rs12365680

Positions:

• chr11-130879164-G-A
• chr11-130879164-G-C

Variant summary

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

The NM_014758.3(SNX19):​c.2846+460C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,046 control chromosomes in the GnomAD database, including 10,064 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (10064 hom., cov: 32)
• Consequence: SNX19 NM_014758.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.06

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 (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX19	NM_014758.3	c.2846+460C>T		intron_variant		ENST00000265909.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX19	ENST00000265909.9	c.2846+460C>T		intron_variant		1	NM_014758.3	P1

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51526 AN: 151928 Hom.: 10063 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.402

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.419

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.338

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.339 AC: 51531 AN: 152046 Hom.: 10064 Cov.: 32 AF XY: 0.343 AC XY: 25500 AN XY: 74312

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.401

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.419

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.335

Alfa AF: 0.391 Hom.: 6463

Bravo AF: 0.333

Asia WGS AF: 0.431 AC: 1498 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.6
DANN	Benign	0.53

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: rs12365680; hg19: chr11-130749059;