6-157906142-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016224.5(SNX9):​c.635C>T​(p.Ala212Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000559 in 1,608,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SNX9
NM_016224.5 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.23
Variant links:
Genes affected
SNX9 (HGNC:14973): (sorting nexin 9) This gene encodes a member of the sorting nexin family. Members of this family contain a phosphoinositide binding domain, and are involved in intracellular trafficking. The encoded protein does not contain a coiled coil region, like some family members, but does contain a SRC homology domain near its N-terminus. The encoded protein is reported to have a variety of interaction partners, including of adaptor protein 2 , dynamin, tyrosine kinase non-receptor 2, Wiskott-Aldrich syndrome-like, and ARP3 actin-related protein 3. The encoded protein is implicated in several stages of intracellular trafficking, including endocytosis, macropinocytosis, and F-actin nucleation. [provided by RefSeq, Jul 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.27082688).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SNX9NM_016224.5 linkc.635C>T p.Ala212Val missense_variant Exon 7 of 18 ENST00000392185.8 NP_057308.1 Q9Y5X1
SNX9XM_011535886.4 linkc.353C>T p.Ala118Val missense_variant Exon 4 of 15 XP_011534188.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SNX9ENST00000392185.8 linkc.635C>T p.Ala212Val missense_variant Exon 7 of 18 1 NM_016224.5 ENSP00000376024.3 Q9Y5X1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152172
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000407
AC:
1
AN:
245826
Hom.:
0
AF XY:
0.00000752
AC XY:
1
AN XY:
132912
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:
0.00000892
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000481
AC:
7
AN:
1456506
Hom.:
0
Cov.:
30
AF XY:
0.00000690
AC XY:
5
AN XY:
724440
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:
0.0000375
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152172
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000860
Hom.:
0
Bravo
AF:
0.0000151

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 24, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.635C>T (p.A212V) alteration is located in exon 7 (coding exon 7) of the SNX9 gene. This alteration results from a C to T substitution at nucleotide position 635, causing the alanine (A) at amino acid position 212 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
0.11
BayesDel_addAF
Benign
-0.078
T
BayesDel_noAF
Benign
-0.35
CADD
Uncertain
23
DANN
Benign
0.88
DEOGEN2
Benign
0.088
T
Eigen
Benign
-0.69
Eigen_PC
Benign
-0.50
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.97
D
M_CAP
Benign
0.040
D
MetaRNN
Benign
0.27
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
1.9
L
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
0.39
N
REVEL
Benign
0.26
Sift
Benign
1.0
T
Sift4G
Benign
0.73
T
Polyphen
0.97
D
Vest4
0.39
MutPred
0.21
Gain of helix (P = 0.062);
MVP
0.54
MPC
1.3
ClinPred
0.47
T
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.097
gMVP
0.37

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: rs759352816; hg19: chr6-158327174; API