Genetic Variant SNX1:p.Pro85Ser (chr15-64112666-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003099.5(SNX1):c.253C>T(p.Pro85Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

SNX1
NM_003099.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.08

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]

SNX1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1638492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX1	NM_003099.5 link	c.253C>T	p.Pro85Ser	missense_variant	Exon 2 of 15	ENST00000559844.6	NP_003090.2	Q13596-1
SNX1	NM_001242933.2 link	c.253C>T	p.Pro85Ser	missense_variant	Exon 2 of 15		NP_001229862.1	Q13596-3
SNX1	NM_148955.4 link	c.253C>T	p.Pro85Ser	missense_variant	Exon 2 of 13		NP_683758.1	Q13596-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNX1	ENST00000559844.6 link	c.253C>T	p.Pro85Ser	missense_variant	Exon 2 of 15	1	NM_003099.5	ENSP00000453785.1		Q13596-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151962

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151962

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74216

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 02, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.253C>T (p.P85S) alteration is located in exon 2 (coding exon 2) of the SNX1 gene. This alteration results from a C to T substitution at nucleotide position 253, causing the proline (P) at amino acid position 85 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

Benign

0.070

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.19

.;T;T;.;T

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.79

T;T;D;D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.16

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.1

L;L;.;L;.

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.5

N;N;.;N;D

REVEL

Benign

0.10

Sift

Uncertain

0.024

D;T;.;T;D

Sift4G

Benign

0.19

T;T;D;T;T

Polyphen

0.087, 0.045

.;B;.;B;.

Vest4

0.34

MutPred

0.56

Gain of phosphorylation at P85 (P = 0.0571);Gain of phosphorylation at P85 (P = 0.0571);Gain of phosphorylation at P85 (P = 0.0571);Gain of phosphorylation at P85 (P = 0.0571);.;

MVP

0.26

MPC

0.28

ClinPred

0.41

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.096

gMVP

0.18

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over