15-64096059-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_003099.5(SNX1):​c.46C>T​(p.Pro16Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000221 in 1,586,830 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 (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

SNX1
NM_003099.5 missense

Scores

4
10
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.47
Variant links:
Genes affected
SNX1 (HGNC:11172): (sorting nexin 1) 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 endosomal protein regulates the cell-surface expression of epidermal growth factor receptor. This protein also has a role in sorting protease-activated receptor-1 from early endosomes to lysosomes. This protein may form oligomeric complexes with family members. This gene results in three transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.34194827).
BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SNX1NM_003099.5 linkc.46C>T p.Pro16Ser missense_variant Exon 1 of 15 ENST00000559844.6 NP_003090.2 Q13596-1
SNX1NM_001242933.2 linkc.46C>T p.Pro16Ser missense_variant Exon 1 of 15 NP_001229862.1 Q13596-3
SNX1NM_148955.4 linkc.46C>T p.Pro16Ser missense_variant Exon 1 of 13 NP_683758.1 Q13596-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SNX1ENST00000559844.6 linkc.46C>T p.Pro16Ser missense_variant Exon 1 of 15 1 NM_003099.5 ENSP00000453785.1 Q13596-1

Frequencies

GnomAD3 genomes
AF:
0.0000328
AC:
5
AN:
152256
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000746
AC:
15
AN:
201114
Hom.:
1
AF XY:
0.0000825
AC XY:
9
AN XY:
109070
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000751
Gnomad NFE exome
AF:
0.000144
Gnomad OTH exome
AF:
0.000194
GnomAD4 exome
AF:
0.0000209
AC:
30
AN:
1434456
Hom.:
0
Cov.:
32
AF XY:
0.0000225
AC XY:
16
AN XY:
711756
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000129
Gnomad4 NFE exome
AF:
0.0000154
Gnomad4 OTH exome
AF:
0.000118
GnomAD4 genome
AF:
0.0000328
AC:
5
AN:
152374
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74518
show subpopulations
Gnomad4 AFR
AF:
0.0000240
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000188
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000508
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.000134
AC:
16

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 22, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.46C>T (p.P16S) alteration is located in exon 1 (coding exon 1) of the SNX1 gene. This alteration results from a C to T substitution at nucleotide position 46, causing the proline (P) at amino acid position 16 to be replaced by a serine (S). 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
Uncertain
0.41
BayesDel_addAF
Benign
-0.093
T
BayesDel_noAF
Benign
-0.12
CADD
Uncertain
25
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.44
.;T;T;.;T
Eigen
Uncertain
0.60
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Benign
0.63
D
LIST_S2
Uncertain
0.91
D;D;D;D;D
M_CAP
Pathogenic
0.37
D
MetaRNN
Benign
0.34
T;T;T;T;T
MetaSVM
Uncertain
-0.26
T
MutationAssessor
Uncertain
2.4
M;M;.;M;.
PrimateAI
Uncertain
0.76
T
PROVEAN
Uncertain
-3.0
D;D;.;D;N
REVEL
Uncertain
0.40
Sift
Pathogenic
0.0
D;D;.;D;D
Sift4G
Pathogenic
0.0
D;D;D;T;D
Polyphen
1.0, 0.99
.;D;.;D;.
Vest4
0.42
MVP
0.64
MPC
0.79
ClinPred
0.80
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.65
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201234536; hg19: chr15-64388258; API