rs495935

chr11-65039806-A-Cchr11-65039806-A-Gchr11-65039806-A-T

Variant summary

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

The NM_013306.5(SNX15):c.*14A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0925 in 1,568,922 control chromosomes in the GnomAD database, including 8,212 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 0.11 (1197 hom., cov: 31)
  • Exomes 𝑓: 0.091 (7015 hom.)
• Consequence: SNX15 NM_013306.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227

Genes affected

SNX15 (HGNC:14978): (sorting nexin 15) This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. Overexpression of this gene results in a decrease in the processing of insulin and hepatocyte growth factor receptors to their mature subunits. This decrease is caused by the mislocalization of furin, the endoprotease responsible for cleavage of insulin and hepatocyte growth factor receptors. This protein is involved in endosomal trafficking from the plasma membrane to recycling endosomes or the trans-Golgi network. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the upstream ADP-ribosylation factor-like 2 (ARL2) gene. [provided by RefSeq, Dec 2010]

ARL2-SNX15 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX15	NM_013306.5	c.*14A>C		3_prime_UTR_variant	8/8	ENST00000377244.8
ARL2-SNX15	NR_037650.2	n.1650A>C		non_coding_transcript_exon_variant	11/11
SNX15	NM_147777.4	c.*14A>C		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX15	ENST00000377244.8	c.*14A>C		3_prime_UTR_variant	8/8	1	NM_013306.5	P1
SNX15	ENST00000526702.1	n.3949A>C		non_coding_transcript_exon_variant	7/7	2
SNX15	ENST00000352068.5			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16936 AN: 151992 Hom.: 1197 Cov.: 31

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.0412

Gnomad EAS AF: 0.0583

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.0494

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0740

Gnomad OTH AF: 0.102

GnomAD3 exomes AF: 0.104 AC: 23774 AN: 229032 Hom.: 1572 AF XY: 0.105 AC XY: 12984 AN XY: 123826

Gnomad AFR exome AF: 0.180

Gnomad AMR exome AF: 0.137

Gnomad ASJ exome AF: 0.0440

Gnomad EAS exome AF: 0.0650

Gnomad SAS exome AF: 0.213

Gnomad FIN exome AF: 0.0553

Gnomad NFE exome AF: 0.0750

Gnomad OTH exome AF: 0.0884

GnomAD4 exome AF: 0.0905 AC: 128235 AN: 1416812 Hom.: 7015 Cov.: 24 AF XY: 0.0931 AC XY: 65721 AN XY: 705860

Gnomad4 AFR exome AF: 0.184

Gnomad4 AMR exome AF: 0.134

Gnomad4 ASJ exome AF: 0.0416

Gnomad4 EAS exome AF: 0.0585

Gnomad4 SAS exome AF: 0.207

Gnomad4 FIN exome AF: 0.0552

Gnomad4 NFE exome AF: 0.0806

Gnomad4 OTH exome AF: 0.0994

GnomAD4 genome AF: 0.112 AC: 16966 AN: 152110 Hom.: 1197 Cov.: 31 AF XY: 0.112 AC XY: 8329 AN XY: 74390

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.0412

Gnomad4 EAS AF: 0.0585

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.0494

Gnomad4 NFE AF: 0.0740

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0887 Hom.: 168

Bravo AF: 0.119

Asia WGS AF: 0.169 AC: 586 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	3.9
Dann	Benign	0.56

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: rs495935; hg19: chr11-64807278;