8-81801580-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152836.3(SNX16):​c.952C>A​(p.Pro318Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.000094 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000021 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SNX16
NM_152836.3 missense

Scores

17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0240
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.03828779).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SNX16NM_152836.3 linkuse as main transcriptc.952C>A p.Pro318Thr missense_variant 8/8 ENST00000345957.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SNX16ENST00000345957.9 linkuse as main transcriptc.952C>A p.Pro318Thr missense_variant 8/81 NM_152836.3 P1P57768-1
SNX16ENST00000353788.8 linkuse as main transcriptc.865C>A p.Pro289Thr missense_variant 7/71 P57768-2
ENST00000524337.1 linkuse as main transcriptn.103+9655G>T intron_variant, non_coding_transcript_variant 5
SNX16ENST00000396330.6 linkuse as main transcriptc.952C>A p.Pro318Thr missense_variant 9/95 P1P57768-1

Frequencies

GnomAD3 genomes
AF:
0.0000864
AC:
11
AN:
127298
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.000232
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000179
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000175
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000146
AC:
3
AN:
205636
Hom.:
0
AF XY:
0.00000885
AC XY:
1
AN XY:
113056
show subpopulations
Gnomad AFR exome
AF:
0.0000710
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000663
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000202
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000206
AC:
26
AN:
1262146
Hom.:
0
Cov.:
28
AF XY:
0.0000221
AC XY:
14
AN XY:
633734
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000262
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000581
Gnomad4 SAS exome
AF:
0.0000260
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000207
Gnomad4 OTH exome
AF:
0.0000191
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000942
AC:
12
AN:
127330
Hom.:
0
Cov.:
30
AF XY:
0.000117
AC XY:
7
AN XY:
59962
show subpopulations
Gnomad4 AFR
AF:
0.000261
Gnomad4 AMR
AF:
0.000179
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000175
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsDec 19, 2023The c.952C>A (p.P318T) alteration is located in exon 9 (coding exon 7) of the SNX16 gene. This alteration results from a C to A substitution at nucleotide position 952, causing the proline (P) at amino acid position 318 to be replaced by a threonine (T). 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
0.064
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
10
DANN
Benign
0.53
Eigen
Benign
-0.89
Eigen_PC
Benign
-0.87
FATHMM_MKL
Benign
0.048
N
LIST_S2
Benign
0.66
T;T;T;.
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.038
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.22
T
PROVEAN
Benign
-1.2
N;N;.;N
REVEL
Benign
0.021
Sift
Benign
0.19
T;T;.;T
Sift4G
Benign
0.74
T;T;T;T
Polyphen
0.0
.;B;.;B
Vest4
0.044
MutPred
0.24
.;Loss of catalytic residue at P318 (P = 0.0056);.;Loss of catalytic residue at P318 (P = 0.0056);
MVP
0.40
MPC
0.27
ClinPred
0.018
T
GERP RS
0.22
Varity_R
0.051
gMVP
0.084

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.

Other links and lift over

dbSNP: rs750152413; hg19: chr8-82713815; API