chr6-157909722-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016224.5(SNX9):​c.763G>A​(p.Ala255Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

SNX9
NM_016224.5 missense

Scores

3
7
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.48
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SNX9NM_016224.5 linkuse as main transcriptc.763G>A p.Ala255Thr missense_variant 8/18 ENST00000392185.8 NP_057308.1
SNX9XM_011535886.4 linkuse as main transcriptc.481G>A p.Ala161Thr missense_variant 5/15 XP_011534188.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SNX9ENST00000392185.8 linkuse as main transcriptc.763G>A p.Ala255Thr missense_variant 8/181 NM_016224.5 ENSP00000376024 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

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 GeneticsMay 26, 2024The c.763G>A (p.A255T) alteration is located in exon 8 (coding exon 8) of the SNX9 gene. This alteration results from a G to A substitution at nucleotide position 763, causing the alanine (A) at amino acid position 255 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
0.29
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.12
T
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D
M_CAP
Benign
0.041
D
MetaRNN
Uncertain
0.64
D
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
-0.35
N
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-1.4
N
REVEL
Uncertain
0.37
Sift
Benign
0.077
T
Sift4G
Benign
0.079
T
Polyphen
1.0
D
Vest4
0.66
MutPred
0.51
Gain of phosphorylation at A255 (P = 0.0279);
MVP
0.58
MPC
2.1
ClinPred
0.97
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.41
gMVP
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-158330754; API