Variant chr8-81801538-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152836.3(SNX16):c.994A>G(p.Ile332Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000313 in 1,596,450 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SNX16
NM_152836.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.01

Variant links:

Genes affected

SNX16 (HGNC:14980): (sorting nexin 16) 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. The protein encoded by this gene associates with late endosome membranes as is involved in tubule formation, cholesterol transport, and transport of tetraspanin CD81. The encoded protein also inhibits cell migration and tumorigenesis. [provided by RefSeq, Jan 2017]

SNX16 links:

SNX16 (HGNC:):

SNX16 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06036222).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX16	NM_152836.3 linkuse as main transcript	c.994A>G	p.Ile332Val	missense_variant	8/8	ENST00000345957.9	NP_690049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SNX16	ENST00000345957.9 linkuse as main transcript	c.994A>G	p.Ile332Val	missense_variant	8/8	1	NM_152836.3	ENSP00000322652.4	P57768-1
SNX16	ENST00000353788.8 linkuse as main transcript	c.907A>G	p.Ile303Val	missense_variant	7/7	1		ENSP00000322631.4	P57768-2
SNX16	ENST00000396330.6 linkuse as main transcript	c.994A>G	p.Ile332Val	missense_variant	9/9	5		ENSP00000379621.2	P57768-1
ENSG00000253334	ENST00000524337.1 linkuse as main transcript	n.103+9613T>C		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

149674

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000667

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1446776

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

720166

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000134

AC:

AN:

149674

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

72820

show subpopulations

Gnomad4 AFR

AF:

0.0000245

Gnomad4 AMR

AF:

0.0000667

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 09, 2024

The c.994A>G (p.I332V) alteration is located in exon 9 (coding exon 7) of the SNX16 gene. This alteration results from a A to G substitution at nucleotide position 994, causing the isoleucine (I) at amino acid position 332 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.018

.;T;T;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.74

T;T;T;.

M_CAP

Benign

0.0085

MetaRNN

Benign

0.060

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.5

.;L;.;L

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.21

N;N;.;N

REVEL

Benign

0.017

Sift

Benign

0.12

T;T;.;T

Sift4G

Benign

0.31

T;T;T;T

Polyphen

0.0050

.;B;.;B

Vest4

0.13

MutPred

0.26

.;Gain of sheet (P = 0.0061);.;Gain of sheet (P = 0.0061);

MVP

0.40

MPC

0.20

ClinPred

0.14

GERP RS

3.6

Varity_R

0.042

gMVP

0.10

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over