Variant chr5-54518167-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001102575.2(SNX18):c.215C>T(p.Pro72Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 1,233,720 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.000014 ( 1 hom. )

Consequence

SNX18
NM_001102575.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.312

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12468916).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX18	NM_001102575.2 link	c.215C>T	p.Pro72Leu	missense_variant	1/2	ENST00000381410.5	NP_001096045.1	Q96RF0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SNX18	ENST00000381410.5 link	c.215C>T	p.Pro72Leu	missense_variant	1/2	1	NM_001102575.2	ENSP00000370817.4	Q96RF0-2
SNX18	ENST00000343017.11 link	c.215C>T	p.Pro72Leu	missense_variant	1/1	6		ENSP00000342276.7	Q96RF0-1
SNX18	ENST00000326277.5 link	c.215C>T	p.Pro72Leu	missense_variant	1/2	2		ENSP00000317332.4	Q96RF0-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000138

AC:

AN:

1233720

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

600230

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000729

Gnomad4 SAS exome

AF:

0.000195

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000297

Gnomad4 OTH exome

AF:

0.0000197

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000843

Hom.:

Bravo

AF:

0.00000378

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

Jan 02, 2024

The c.215C>T (p.P72L) 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 215, causing the proline (P) at amino acid position 72 to be replaced by a leucine (L). 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

0.093

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0066

.;.;T

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.81

T;T;T

M_CAP

Pathogenic

0.40

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N;N

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

0.11

N;N;N

REVEL

Benign

0.051

Sift

Benign

0.051

T;T;T

Sift4G

Benign

0.22

T;T;T

Polyphen

0.13, 0.20

.;B;B

Vest4

0.084

MutPred

0.26

Gain of stability (P = 0.0205);Gain of stability (P = 0.0205);Gain of stability (P = 0.0205);

MVP

0.45

ClinPred

0.084

GERP RS

2.3

Varity_R

0.058

gMVP

0.19

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