6-157909983-T-C

Variant summary

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

The NM_016224.5(SNX9):​c.907T>C​(p.Ser303Pro) variant causes a missense change. 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

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.57
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.907T>C p.Ser303Pro missense_variant 9/18 ENST00000392185.8 NP_057308.1
SNX9XM_011535886.4 linkuse as main transcriptc.625T>C p.Ser209Pro missense_variant 6/15 XP_011534188.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SNX9ENST00000392185.8 linkuse as main transcriptc.907T>C p.Ser303Pro missense_variant 9/181 NM_016224.5 ENSP00000376024 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
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 GeneticsFeb 13, 2023The c.907T>C (p.S303P) alteration is located in exon 9 (coding exon 9) of the SNX9 gene. This alteration results from a T to C substitution at nucleotide position 907, causing the serine (S) at amino acid position 303 to be replaced by a proline (P). 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
0.21
BayesDel_addAF
Benign
-0.078
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.074
T
Eigen
Uncertain
0.29
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.87
D
M_CAP
Benign
0.010
T
MetaRNN
Uncertain
0.51
D
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
-1.1
N
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.65
T
PROVEAN
Benign
-0.19
N
REVEL
Benign
0.20
Sift
Benign
0.46
T
Sift4G
Benign
0.15
T
Polyphen
1.0
D
Vest4
0.61
MutPred
0.61
Loss of phosphorylation at S303 (P = 0.1721);
MVP
0.56
MPC
1.8
ClinPred
0.75
D
GERP RS
4.4
Varity_R
0.23
gMVP
0.76

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: chr6-158331015; API