6-157940913-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_016224.5(SNX9):​c.1679T>C​(p.Ile560Thr) 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: 33)

Consequence

SNX9
NM_016224.5 missense

Scores

5
7
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.58
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 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.878

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SNX9NM_016224.5 linkuse as main transcriptc.1679T>C p.Ile560Thr missense_variant 17/18 ENST00000392185.8 NP_057308.1
SNX9XM_011535886.4 linkuse as main transcriptc.1397T>C p.Ile466Thr missense_variant 14/15 XP_011534188.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SNX9ENST00000392185.8 linkuse as main transcriptc.1679T>C p.Ile560Thr missense_variant 17/181 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 GeneticsAug 22, 2023The c.1679T>C (p.I560T) alteration is located in exon 17 (coding exon 17) of the SNX9 gene. This alteration results from a T to C substitution at nucleotide position 1679, causing the isoleucine (I) at amino acid position 560 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
Pathogenic
0.93
BayesDel_addAF
Uncertain
0.079
D
BayesDel_noAF
Benign
-0.12
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
T
Eigen
Pathogenic
0.69
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.97
D
M_CAP
Uncertain
0.20
D
MetaRNN
Pathogenic
0.88
D
MetaSVM
Benign
-0.71
T
MutationAssessor
Benign
1.9
L
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.90
D
PROVEAN
Uncertain
-2.4
N
REVEL
Uncertain
0.39
Sift
Benign
0.031
D
Sift4G
Benign
0.17
T
Polyphen
1.0
D
Vest4
0.90
MutPred
0.68
Loss of stability (P = 0.0012);
MVP
0.24
MPC
0.90
ClinPred
0.96
D
GERP RS
5.9
Varity_R
0.58
gMVP
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: chr6-158361945; API