Variant 8-81801565-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.967A>G(p.Ser323Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,396,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

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: 0.320

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=0.067712724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX16	NM_152836.3 linkuse as main transcript	c.967A>G	p.Ser323Gly	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.967A>G	p.Ser323Gly	missense_variant	8/8	1	NM_152836.3	ENSP00000322652.4	P57768-1
SNX16	ENST00000353788.8 linkuse as main transcript	c.880A>G	p.Ser294Gly	missense_variant	7/7	1		ENSP00000322631.4	P57768-2
SNX16	ENST00000396330.6 linkuse as main transcript	c.967A>G	p.Ser323Gly	missense_variant	9/9	5		ENSP00000379621.2	P57768-1
ENSG00000253334	ENST00000524337.1 linkuse as main transcript	n.103+9640T>C		intron_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1396692

Hom.:

Cov.:

AF XY:

0.00000287

AC XY:

AN XY:

696568

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:

0.00000279

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Sep 14, 2022

The c.967A>G (p.S323G) 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 967, causing the serine (S) at amino acid position 323 to be replaced by a glycine (G). 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

0.059

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

6.8

DANN

Uncertain

0.98

DEOGEN2

Benign

0.028

.;T;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.082

LIST_S2

Benign

0.53

T;T;T;.

M_CAP

Benign

0.0040

MetaRNN

Benign

0.068

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

.;L;.;L

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.68

N;N;.;N

REVEL

Benign

0.12

Sift

Benign

0.25

T;T;.;T

Sift4G

Benign

0.41

T;T;T;T

Polyphen

0.0

.;B;.;B

Vest4

0.086

MutPred

0.15

.;Loss of phosphorylation at S323 (P = 0.0239);.;Loss of phosphorylation at S323 (P = 0.0239);

MVP

0.36

MPC

0.22

ClinPred

0.93

GERP RS

-1.5

Varity_R

0.033

gMVP

0.11

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