chr6-157938637-C-G
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_016224.5(SNX9):āc.1538C>Gā(p.Ala513Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000125 in 1,603,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00011 ( 0 hom., cov: 33)
Exomes š: 0.0000021 ( 0 hom. )
Consequence
SNX9
NM_016224.5 missense
NM_016224.5 missense
Scores
1
9
9
Clinical Significance
Conservation
PhyloP100: 4.52
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 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.4065165).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SNX9 | NM_016224.5 | c.1538C>G | p.Ala513Gly | missense_variant | 16/18 | ENST00000392185.8 | NP_057308.1 | |
SNX9 | XM_011535886.4 | c.1256C>G | p.Ala419Gly | missense_variant | 13/15 | XP_011534188.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SNX9 | ENST00000392185.8 | c.1538C>G | p.Ala513Gly | missense_variant | 16/18 | 1 | NM_016224.5 | ENSP00000376024 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000112 AC: 17AN: 152040Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250784Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135538
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GnomAD4 exome AF: 0.00000207 AC: 3AN: 1451690Hom.: 0 Cov.: 28 AF XY: 0.00000277 AC XY: 2AN XY: 722928
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GnomAD4 genome AF: 0.000112 AC: 17AN: 152158Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74378
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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 submitter | clinical testing | Ambry Genetics | Nov 08, 2021 | The c.1538C>G (p.A513G) alteration is located in exon 16 (coding exon 16) of the SNX9 gene. This alteration results from a C to G substitution at nucleotide position 1538, causing the alanine (A) at amino acid position 513 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at