Variant chr5-54518125-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001102575.2(SNX18):c.173T>A(p.Val58Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SNX18
NM_001102575.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.77

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX18	NM_001102575.2 link	c.173T>A	p.Val58Glu	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.173T>A	p.Val58Glu	missense_variant	1/2	1	NM_001102575.2	ENSP00000370817.4	Q96RF0-2
SNX18	ENST00000343017.11 link	c.173T>A	p.Val58Glu	missense_variant	1/1	6		ENSP00000342276.7	Q96RF0-1
SNX18	ENST00000326277.5 link	c.173T>A	p.Val58Glu	missense_variant	1/2	2		ENSP00000317332.4	Q96RF0-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1302492

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

640314

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:

0.00

Gnomad4 OTH exome

AF:

0.00

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

Nov 21, 2023

The c.173T>A (p.V58E) alteration is located in exon 1 (coding exon 1) of the SNX18 gene. This alteration results from a T to A substitution at nucleotide position 173, causing the valine (V) at amino acid position 58 to be replaced by a glutamic acid (E). 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

0.80

BayesDel_addAF

Uncertain

0.015

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

.;.;T

Eigen

Benign

0.070

Eigen_PC

Benign

0.071

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.76

T;T;T

M_CAP

Pathogenic

0.39

MetaRNN

Uncertain

0.70

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.72

N;N;N

PrimateAI

Pathogenic

0.95

PROVEAN

Uncertain

-3.3

D;D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.044

D;D;D

Polyphen

0.96, 0.92

.;D;P

Vest4

0.62

MutPred

0.63

Gain of disorder (P = 0.0067);Gain of disorder (P = 0.0067);Gain of disorder (P = 0.0067);

MVP

0.45

ClinPred

0.98

GERP RS

3.5

Varity_R

0.91

gMVP

0.52

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over