Variant 8-81839793-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_152836.3(SNX16):c.194C>T(p.Ser65Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

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: 6.23

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX16	NM_152836.3 linkuse as main transcript	c.194C>T	p.Ser65Leu	missense_variant	2/8	ENST00000345957.9	NP_690049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX16	ENST00000345957.9 linkuse as main transcript	c.194C>T	p.Ser65Leu	missense_variant	2/8	1	NM_152836.3	ENSP00000322652.4		P57768-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251340

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461360

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727012

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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 16, 2023

The c.194C>T (p.S65L) alteration is located in exon 3 (coding exon 1) of the SNX16 gene. This alteration results from a C to T substitution at nucleotide position 194, causing the serine (S) at amino acid position 65 to be replaced by a leucine (L). 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

0.079

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.034

.;T;T;T;.;T;.;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

D;D;D;.;D;D;D;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.28

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Uncertain

2.2

M;M;.;M;.;.;.;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.3

N;N;.;N;D;N;D;D

REVEL

Benign

0.19

Sift

Uncertain

0.0020

D;D;.;D;D;D;D;D

Sift4G

Uncertain

0.011

D;D;D;D;.;.;.;.

Polyphen

0.97

.;D;.;D;.;.;.;.

Vest4

0.36

MutPred

0.25

Loss of phosphorylation at S65 (P = 0.084);Loss of phosphorylation at S65 (P = 0.084);Loss of phosphorylation at S65 (P = 0.084);Loss of phosphorylation at S65 (P = 0.084);Loss of phosphorylation at S65 (P = 0.084);Loss of phosphorylation at S65 (P = 0.084);Loss of phosphorylation at S65 (P = 0.084);Loss of phosphorylation at S65 (P = 0.084);

MVP

0.66

MPC

0.37

ClinPred

0.85

GERP RS

5.9

Varity_R

0.19

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.27

Position offset: 46

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