17-48119026-C-A

Variant summary

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

The NM_013323.3(SNX11):​c.379C>A​(p.Gln127Lys) 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: 32)

Consequence

SNX11
NM_013323.3 missense

Scores

5
11
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.52
Variant links:
Genes affected
SNX11 (HGNC:14975): (sorting nexin 11) This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. This protein does not contain a coiled coil region, like some family members. This gene encodes a protein of unknown function. This gene results in two transcript variants differing in the 5' UTR, but encoding the same protein. [provided by RefSeq, Jul 2008]

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, 0.789

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SNX11NM_013323.3 linkc.379C>A p.Gln127Lys missense_variant Exon 6 of 7 ENST00000359238.7 NP_037455.2 Q9Y5W9-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SNX11ENST00000359238.7 linkc.379C>A p.Gln127Lys missense_variant Exon 6 of 7 1 NM_013323.3 ENSP00000352175.2 Q9Y5W9-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 05, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.379C>A (p.Q127K) alteration is located in exon 7 (coding exon 5) of the SNX11 gene. This alteration results from a C to A substitution at nucleotide position 379, causing the glutamine (Q) at amino acid position 127 to be replaced by a lysine (K). 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
0.99
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.060
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.13
T;.;T;T;.;T;.
Eigen
Pathogenic
0.92
Eigen_PC
Pathogenic
0.87
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.95
D;.;.;D;D;D;D
M_CAP
Benign
0.068
D
MetaRNN
Pathogenic
0.79
D;D;D;D;D;D;D
MetaSVM
Uncertain
-0.23
T
MutationAssessor
Uncertain
2.9
.;.;M;M;.;.;.
PrimateAI
Uncertain
0.78
T
PROVEAN
Uncertain
-3.7
.;.;D;D;.;.;.
REVEL
Uncertain
0.54
Sift
Uncertain
0.0010
.;.;D;D;.;.;.
Sift4G
Pathogenic
0.0
D;D;D;D;D;D;D
Polyphen
1.0
.;.;D;D;.;.;.
Vest4
0.81, 0.80, 0.80, 0.78
MutPred
0.56
Gain of loop (P = 0.0079);.;Gain of loop (P = 0.0079);Gain of loop (P = 0.0079);.;Gain of loop (P = 0.0079);Gain of loop (P = 0.0079);
MVP
0.77
MPC
0.60
ClinPred
0.99
D
GERP RS
5.5
Varity_R
0.92
gMVP
0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-46196388; API