NM_013306.5:c.464G>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_013306.5(SNX15):c.464G>A(p.Arg155Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000194 in 1,181,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

SNX15
NM_013306.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.164

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.033277184).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013306.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SNX15	NM_013306.5	MANE Select	c.464G>A	p.Arg155Gln	missense	Exon 5 of 8	NP_037438.2
SNX15	NM_147777.4		c.464G>A	p.Arg155Gln	missense	Exon 5 of 7	NP_680086.2
ARL2-SNX15	NR_037650.2		n.1071G>A		non_coding_transcript_exon	Exon 8 of 11

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNX15	ENST00000377244.8	TSL:1 MANE Select	c.464G>A	p.Arg155Gln	missense	Exon 5 of 8	ENSP00000366452.3	Q9NRS6-1
ARL2-SNX15	ENST00000301886.3	TSL:2	n.*681G>A		non_coding_transcript_exon	Exon 8 of 11	ENSP00000476630.1	V9GYD0
ARL2-SNX15	ENST00000301886.3	TSL:2	n.*681G>A		3_prime_UTR	Exon 8 of 11	ENSP00000476630.1	V9GYD0

Frequencies

GnomAD3 genomes

AF:

0.000123

AC:

AN:

137798

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000261

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000709

Gnomad ASJ

AF:

0.000307

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000222

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000123

AC:

AN:

202894

AF XY:

0.000171

show subpopulations

Gnomad AFR exome

AF:

0.0000884

Gnomad AMR exome

AF:

0.0000688

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000125

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000226

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000203

AC:

212

AN:

1043502

Hom.:

Cov.:

AF XY:

0.000217

AC XY:

113

AN XY:

521726

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23756

American (AMR)

AF:

0.0000592

AC:

AN:

33784

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16560

East Asian (EAS)

AF:

0.000588

AC:

AN:

18708

South Asian (SAS)

AF:

0.00

AC:

AN:

76262

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31380

Middle Eastern (MID)

AF:

0.000780

AC:

AN:

3848

European-Non Finnish (NFE)

AF:

0.000231

AC:

185

AN:

799942

Other (OTH)

AF:

0.000280

AC:

AN:

39262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000123

AC:

AN:

137882

Hom.:

Cov.:

AF XY:

0.000120

AC XY:

AN XY:

66898

show subpopulations

African (AFR)

AF:

0.0000260

AC:

AN:

38428

American (AMR)

AF:

0.0000707

AC:

AN:

14140

Ashkenazi Jewish (ASJ)

AF:

0.000307

AC:

AN:

3256

East Asian (EAS)

AF:

0.00

AC:

AN:

4106

South Asian (SAS)

AF:

0.00

AC:

AN:

3730

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8258

Middle Eastern (MID)

AF:

0.00

AC:

AN:

278

European-Non Finnish (NFE)

AF:

0.000222

AC:

AN:

62948

Other (OTH)

AF:

0.00

AC:

AN:

1932

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000133

Hom.:

Bravo

AF:

0.000144

ExAC

AF:

0.0000830

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.014

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.85

M_CAP

Benign

0.0043

MetaRNN

Benign

0.033

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

PhyloP100

0.16

PROVEAN

Benign

-0.42

REVEL

Benign

0.021

Sift

Benign

0.56

Sift4G

Benign

0.30

Polyphen

0.0070

Vest4

0.14

MVP

0.14

MPC

0.29

ClinPred

0.014

GERP RS

-2.0

Varity_R

0.015

gMVP

0.32

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over