5-122819018-G-C

Position:

• chr5-122819018-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003100.4(SNX2):​c.1207G>C​(p.Val403Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SNX2 NM_003100.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.19

Genes affected

SNX2 (HGNC:11173): (sorting nexin 2) This gene belongs to the sorting nexin family whose members contain the phosphoinositide-binding phox (PX) domain. The encoded protein is a component of the retromer complex which plays a role in protein sorting in the endocytic pathway. This protein may form oligomeric complexes with other family members. Alternate splicing results in multiple transcript variants of this gene. Pseudogenes associated with this gene are located on chromosomes 1 and 7. [provided by RefSeq, May 2013]

SNX2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.757

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX2	NM_003100.4	c.1207G>C	p.Val403Leu	missense_variant	11/15	ENST00000379516.7	NP_003091.2
SNX2	NM_001278199.1	c.856G>C	p.Val286Leu	missense_variant	11/15		NP_001265128.1
LOC105379154	XR_007058917.1	n.1176+25356C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX2	ENST00000379516.7	c.1207G>C	p.Val403Leu	missense_variant	11/15	1	NM_003100.4	ENSP00000368831.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

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

Aug 14, 2024

The c.1207G>C (p.V403L) alteration is located in exon 11 (coding exon 11) of the SNX2 gene. This alteration results from a G to C substitution at nucleotide position 1207, causing the valine (V) at amino acid position 403 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	Uncertain	0.52
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.049	D
MetaRNN	Pathogenic	0.76	D;D
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.5	L;.
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.3	N;N
REVEL	Uncertain	0.39
Sift	Benign	0.049	D;T
Sift4G	Benign	0.30	T;T
Polyphen		0.095	B;.
Vest4		0.72
MutPred		0.78		Loss of catalytic residue at V403 (P = 0.0221);.;
MVP		0.62
MPC		0.20
ClinPred		0.90	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.39
gMVP		0.67

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: chr5-122154713;