chr5-54518290-C-T

Position:

• chr5-54518290-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001102575.2(SNX18):​c.338C>T​(p.Ala113Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000148 in 1,352,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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: 0.0000015 (0 hom.)
• Consequence: SNX18 NM_001102575.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.399

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]

ACMG classification

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=0.097628474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX18	NM_001102575.2	c.338C>T	p.Ala113Val	missense_variant	1/2	ENST00000381410.5	NP_001096045.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX18	ENST00000381410.5	c.338C>T	p.Ala113Val	missense_variant	1/2	1	NM_001102575.2	ENSP00000370817.4
SNX18	ENST00000343017.11	c.338C>T	p.Ala113Val	missense_variant	1/1	6		ENSP00000342276.7
SNX18	ENST00000326277.5	c.338C>T	p.Ala113Val	missense_variant	1/2	2		ENSP00000317332.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000148 AC: 2 AN: 1352908 Hom.: 0 Cov.: 84 AF XY: 0.00000300 AC XY: 2 AN XY: 666474

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000326

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.41e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.338C>T (p.A113V) 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 338, causing the alanine (A) at amino acid position 113 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	Benign	0.074
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.018	.;.;T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.45
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.78	T;T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.098	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N;N
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.99	N;N;N
REVEL	Benign	0.028
Sift	Benign	0.060	T;T;T
Sift4G	Benign	0.12	T;T;T
Polyphen		0.025, 0.033	.;B;B
Vest4		0.11
MutPred		0.19		Loss of relative solvent accessibility (P = 0.0404);Loss of relative solvent accessibility (P = 0.0404);Loss of relative solvent accessibility (P = 0.0404);
MVP		0.35
ClinPred		0.15	T
GERP RS		2.4
Varity_R		0.080
gMVP		0.17

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

Other links and lift over

dbSNP: rs1280821085; hg19: chr5-53814120;