6-157901933-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_016224.5(SNX9):​c.508G>T​(p.Asp170Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

SNX9
NM_016224.5 missense

Scores

4
12
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.12
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.826

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SNX9NM_016224.5 linkuse as main transcriptc.508G>T p.Asp170Tyr missense_variant 6/18 ENST00000392185.8 NP_057308.1
SNX9XM_011535886.4 linkuse as main transcriptc.226G>T p.Asp76Tyr missense_variant 3/15 XP_011534188.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SNX9ENST00000392185.8 linkuse as main transcriptc.508G>T p.Asp170Tyr missense_variant 6/181 NM_016224.5 ENSP00000376024 P1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
31

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 GeneticsApr 25, 2022The c.508G>T (p.D170Y) alteration is located in exon 6 (coding exon 6) of the SNX9 gene. This alteration results from a G to T substitution at nucleotide position 508, causing the aspartic acid (D) at amino acid position 170 to be replaced by a tyrosine (Y). 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
Uncertain
0.36
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.15
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.69
D
Eigen
Uncertain
0.59
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.081
D
MetaRNN
Pathogenic
0.83
D
MetaSVM
Benign
-0.73
T
MutationAssessor
Uncertain
2.3
M
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.65
T
PROVEAN
Uncertain
-3.8
D
REVEL
Uncertain
0.40
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.0020
D
Polyphen
1.0
D
Vest4
0.82
MutPred
0.17
Gain of phosphorylation at D170 (P = 0.0365);
MVP
0.33
MPC
0.21
ClinPred
0.98
D
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.82
gMVP
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs760959192; hg19: chr6-158322965; API