Variant 5-54518191-A-G 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.239A>G(p.Asn80Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000317 in 1,389,554 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 0.000092 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

SNX18
NM_001102575.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.91

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:

Genome browser will be placed here

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=0.21753085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX18	NM_001102575.2 linkuse as main transcript	c.239A>G	p.Asn80Ser	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.239A>G	p.Asn80Ser	missense_variant	1/2	1	NM_001102575.2	P1	Q96RF0-2
SNX18	ENST00000343017.11 linkuse as main transcript	c.239A>G	p.Asn80Ser	missense_variant	1/1				Q96RF0-1
SNX18	ENST00000326277.5 linkuse as main transcript	c.239A>G	p.Asn80Ser	missense_variant	1/2	2			Q96RF0-3

Frequencies

GnomAD3 genomes

AF:

0.0000923

AC:

AN:

151714

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00321

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000242

AC:

AN:

1237732

Hom.:

Cov.:

AF XY:

0.0000232

AC XY:

AN XY:

602768

show subpopulations

Gnomad4 AFR exome

AF:

0.0000829

Gnomad4 AMR exome

AF:

0.000346

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000361

Gnomad4 SAS exome

AF:

0.0000177

Gnomad4 FIN exome

AF:

0.0000309

Gnomad4 NFE exome

AF:

0.0000178

Gnomad4 OTH exome

AF:

0.0000590

GnomAD4 genome

AF:

0.0000922

AC:

AN:

151822

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74212

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000982

ExAC

AF:

0.0000232

AC:

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

Jun 03, 2022

The c.239A>G (p.N80S) alteration is located in exon 1 (coding exon 1) of the SNX18 gene. This alteration results from a A to G substitution at nucleotide position 239, causing the asparagine (N) at amino acid position 80 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

0.15

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.015

.;.;T

Eigen

Benign

0.053

Eigen_PC

Benign

0.063

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.78

T;T;T

M_CAP

Pathogenic

0.33

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N;N

MutationTaster

Benign

0.99

D;D

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.64

N;N;N

REVEL

Benign

0.096

Sift

Benign

0.27

T;T;T

Sift4G

Benign

0.47

T;T;T

Polyphen

0.96, 0.99

.;D;D

Vest4

0.27

MutPred

0.21

Gain of phosphorylation at N80 (P = 0.0077);Gain of phosphorylation at N80 (P = 0.0077);Gain of phosphorylation at N80 (P = 0.0077);

MVP

0.58

ClinPred

0.85

GERP RS

3.4

Varity_R

0.068

gMVP

0.28

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