rs2236711

Positions:

• chr11-130869389-G-A

Variant summary

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

The NM_014758.3(SNX19):​c.*9033C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 152,064 control chromosomes in the GnomAD database, including 14,825 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 0.44 (14825 hom., cov: 34)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: SNX19 NM_014758.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.981

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]

ENSG00000255455 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX19	NM_014758.3	c.*9033C>T		3_prime_UTR_variant	11/11	ENST00000265909.9	NP_055573.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX19	ENST00000265909	c.*9033C>T		3_prime_UTR_variant	11/11	1	NM_014758.3	ENSP00000265909.4
ENSG00000255455	ENST00000525716.2	n.859C>T		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66485 AN: 151944 Hom.: 14827 Cov.: 34

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.427

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 AFR exome AF: 0.500

GnomAD4 genome AF: 0.437 AC: 66504 AN: 152062 Hom.: 14825 Cov.: 34 AF XY: 0.440 AC XY: 32695 AN XY: 74336

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.561

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.423

Alfa AF: 0.462 Hom.: 7713

Bravo AF: 0.437

Asia WGS AF: 0.525 AC: 1826 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.23
DANN	Benign	0.41

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2236711; hg19: chr11-130739284;