Variant 5-54518110-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001102575.2(SNX18):c.158C>T(p.Ala53Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000295 in 1,357,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

SNX18
NM_001102575.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.16

Variant links:

Genes affected

SNX18 (HGNC:19245): (sorting nexin 18) 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, but contains a SH3 domain. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SNX18 links:

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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, 0.843

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX18	NM_001102575.2 linkuse as main transcript	c.158C>T	p.Ala53Val	missense_variant	1/2	ENST00000381410.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX18	ENST00000381410.5 linkuse as main transcript	c.158C>T	p.Ala53Val	missense_variant	1/2	1	NM_001102575.2	P1	Q96RF0-2
SNX18	ENST00000343017.11 linkuse as main transcript	c.158C>T	p.Ala53Val	missense_variant	1/1				Q96RF0-1
SNX18	ENST00000326277.5 linkuse as main transcript	c.158C>T	p.Ala53Val	missense_variant	1/2	2			Q96RF0-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000988

AC:

AN:

101198

Hom.:

AF XY:

0.00

AC XY:

AN XY:

57700

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:

0.00

Gnomad NFE exome

AF:

0.0000259

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000295

AC:

AN:

1357184

Hom.:

Cov.:

AF XY:

0.00000149

AC XY:

AN XY:

670638

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:

0.00

Gnomad4 NFE exome

AF:

0.00000281

Gnomad4 OTH exome

AF:

0.0000177

GnomAD4 genome

Cov.:

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

May 23, 2023

The c.158C>T (p.A53V) alteration is located in exon 1 (coding exon 1) of the SNX18 gene. This alteration results from a C to T substitution at nucleotide position 158, causing the alanine (A) at amino acid position 53 to be replaced by a valine (V). 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

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.057

.;.;T

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Benign

0.60

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Pathogenic

0.61

MetaRNN

Pathogenic

0.84

D;D;D

MetaSVM

Benign

-0.53

MutationAssessor

Benign

1.9

L;L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.26

Sift

Benign

0.058

T;D;D

Sift4G

Benign

0.31

T;T;T

Polyphen

1.0, 0.89

.;D;P

Vest4

0.74

MutPred

0.52

Loss of disorder (P = 0.1174);Loss of disorder (P = 0.1174);Loss of disorder (P = 0.1174);

MVP

0.75

ClinPred

0.95

GERP RS

3.5

Varity_R

0.36

gMVP

0.62

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

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

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