5-54518331-C-A

Position:

• chr5-54518331-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001102575.2(SNX18):​c.379C>A​(p.Pro127Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: SNX18 NM_001102575.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.854

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06229669).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX18	NM_001102575.2	c.379C>A	p.Pro127Thr	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.379C>A	p.Pro127Thr	missense_variant	1/2	1	NM_001102575.2	ENSP00000370817.4
SNX18	ENST00000343017.11	c.379C>A	p.Pro127Thr	missense_variant	1/1	6		ENSP00000342276.7
SNX18	ENST00000326277.5	c.379C>A	p.Pro127Thr	missense_variant	1/2	2		ENSP00000317332.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 84

GnomAD4 genome Cov.: 34

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

Dec 17, 2023

The c.379C>A (p.P127T) alteration is located in exon 1 (coding exon 1) of the SNX18 gene. This alteration results from a C to A substitution at nucleotide position 379, causing the proline (P) at amino acid position 127 to be replaced by a threonine (T). 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	0.079
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.7
DANN	Benign	0.84
DEOGEN2	Benign	0.0069	.;.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.61	T;T;T
M_CAP	Uncertain	0.098	D
MetaRNN	Benign	0.062	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N;N;N
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.68	N;N;N
REVEL	Benign	0.014
Sift	Benign	0.20	T;T;T
Sift4G	Benign	0.26	T;T;T
Polyphen		0.21, 0.0	.;B;B
Vest4		0.052
MutPred		0.23		Gain of glycosylation at P127 (P = 0.0218);Gain of glycosylation at P127 (P = 0.0218);Gain of glycosylation at P127 (P = 0.0218);
MVP		0.23
ClinPred		0.022	T
GERP RS		0.60
Varity_R		0.048
gMVP		0.22

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.

Other links and lift over

hg19: chr5-53814161;