6-157896831-G-A

Variant summary

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

The NM_016224.5(SNX9):​c.305G>A​(p.Gly102Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000201 in 1,612,510 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00024 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

SNX9
NM_016224.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.41
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 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=0.006731242).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SNX9NM_016224.5 linkuse as main transcriptc.305G>A p.Gly102Asp missense_variant 5/18 ENST00000392185.8 NP_057308.1
SNX9XM_011535886.4 linkuse as main transcriptc.23G>A p.Gly8Asp missense_variant 2/15 XP_011534188.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SNX9ENST00000392185.8 linkuse as main transcriptc.305G>A p.Gly102Asp missense_variant 5/181 NM_016224.5 ENSP00000376024 P1

Frequencies

GnomAD3 genomes
AF:
0.000243
AC:
37
AN:
152198
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000393
Gnomad ASJ
AF:
0.00547
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000353
AC:
88
AN:
249256
Hom.:
1
AF XY:
0.000386
AC XY:
52
AN XY:
134814
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000713
Gnomad ASJ exome
AF:
0.00460
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000660
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000115
Gnomad OTH exome
AF:
0.000492
GnomAD4 exome
AF:
0.000197
AC:
287
AN:
1460194
Hom.:
1
Cov.:
31
AF XY:
0.000211
AC XY:
153
AN XY:
726452
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
Gnomad4 AMR exome
AF:
0.000635
Gnomad4 ASJ exome
AF:
0.00429
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000163
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000963
Gnomad4 OTH exome
AF:
0.000365
GnomAD4 genome
AF:
0.000243
AC:
37
AN:
152316
Hom.:
0
Cov.:
32
AF XY:
0.000309
AC XY:
23
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000392
Gnomad4 ASJ
AF:
0.00547
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000284
Hom.:
0
Bravo
AF:
0.000257
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000465
AC:
4
ExAC
AF:
0.000239
AC:
29
EpiCase
AF:
0.000109
EpiControl
AF:
0.000178

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 GeneticsAug 23, 2021The c.305G>A (p.G102D) alteration is located in exon 5 (coding exon 5) of the SNX9 gene. This alteration results from a G to A substitution at nucleotide position 305, causing the glycine (G) at amino acid position 102 to be replaced by an aspartic acid (D). 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
0.12
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
19
DANN
Uncertain
0.98
DEOGEN2
Benign
0.084
T
Eigen
Benign
-0.57
Eigen_PC
Benign
-0.43
FATHMM_MKL
Benign
0.61
D
LIST_S2
Benign
0.78
T
M_CAP
Benign
0.0075
T
MetaRNN
Benign
0.0067
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
1.0
D;N;N
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.21
N
REVEL
Benign
0.10
Sift
Benign
0.22
T
Sift4G
Benign
0.40
T
Polyphen
0.0090
B
Vest4
0.24
MVP
0.33
MPC
0.068
ClinPred
0.033
T
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.037
gMVP
0.44

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: rs144624939; hg19: chr6-158317863; API