rs1054869

chr11-130872735-G-Achr11-130872735-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.*5687C>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 151,944 control chromosomes in the GnomAD database, including 14,831 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 (14831 hom., cov: 32)
• Consequence: SNX19 NM_014758.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX19	NM_014758.3	c.*5687C>T		3_prime_UTR_variant	11/11	ENST00000265909.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX19	ENST00000265909.9	c.*5687C>T		3_prime_UTR_variant	11/11	1	NM_014758.3	P1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66457 AN: 151826 Hom.: 14833 Cov.: 32

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.437 AC: 66475 AN: 151944 Hom.: 14831 Cov.: 32 AF XY: 0.440 AC XY: 32662 AN XY: 74248

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.501

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.560

Gnomad4 FIN AF: 0.436

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.426

Alfa AF: 0.463 Hom.: 7541

Bravo AF: 0.437

Asia WGS AF: 0.529 AC: 1839 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	5.9
Dann	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1054869; hg19: chr11-130742630;