Variant rs495935 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.227

Variant links:

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]

SNX15 links:

ARL2-SNX15 (HGNC:49197): (ARL2-SNX15 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring ADP-ribosylation factor-like 2 (ARL2) and sorting nexin 15 (SNX15) genes on chromosome 11. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is therefore unlikely to produce a protein product. [provided by RefSeq, Dec 2010]

ARL2-SNX15 links:

SNX15 (HGNC:):

SNX15 links:

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ACMG classification

Classification made for transcript

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	Effect	#exon/exons	MANE	Protein	UniProt
SNX15	NM_013306.5 linkuse as main transcript	c.*14A>C	3_prime_UTR_variant	8/8	ENST00000377244.8	NP_037438.2	Q9NRS6-1E5KQS5
SNX15	NM_147777.4 linkuse as main transcript	c.*14A>C	3_prime_UTR_variant	7/7		NP_680086.2	Q9NRS6-2
ARL2-SNX15	NR_037650.2 linkuse as main transcript	n.1650A>C	non_coding_transcript_exon_variant	11/11

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SNX15	ENST00000377244.8 linkuse as main transcript	c.*14A>C	3_prime_UTR_variant	8/8	1	NM_013306.5	ENSP00000366452.3	Q9NRS6-1
ARL2-SNX15	ENST00000301886.3 linkuse as main transcript	n.*1260A>C	non_coding_transcript_exon_variant	11/11	2		ENSP00000476630.1	V9GYD0
ARL2-SNX15	ENST00000301886.3 linkuse as main transcript	n.*1260A>C	3_prime_UTR_variant	11/11	2		ENSP00000476630.1	V9GYD0

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16936

AN:

151992

Hom.:

1197

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0931

AC XY:

65721

AN XY:

705860

show subpopulations

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.:

AF XY:

0.112

AC XY:

8329

AN XY:

74390

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over