6-108222963-T-C

Position:

• chr6-108222963-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The ENST00000230085.13(SNX3):​c.245A>G​(p.Glu82Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SNX3 ENST00000230085.13 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.02

Genes affected

SNX3 (HGNC:11174): (sorting nexin 3) 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 most family members. This protein interacts with phosphatidylinositol-3-phosphate, and is involved in protein trafficking. A pseudogene of this gene is present on the sex chromosomes. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.872

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX3	NM_003795.6	c.245A>G	p.Glu82Gly	missense_variant	2/4	ENST00000230085.13	NP_003786.1
SNX3	NM_001300929.2	c.179A>G	p.Glu60Gly	missense_variant	2/4		NP_001287858.1
SNX3	NM_001300928.2	c.245A>G	p.Glu82Gly	missense_variant	2/3		NP_001287857.1
SNX3	NM_152827.4	c.163-8341A>G		intron_variant			NP_690040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX3	ENST00000230085.13	c.245A>G	p.Glu82Gly	missense_variant	2/4	1	NM_003795.6	ENSP00000230085	P1
SNX3	ENST00000426155.6	c.163-8341A>G		intron_variant		1		ENSP00000401779
SNX3	ENST00000349379.5	c.179A>G	p.Glu60Gly	missense_variant	2/4	2		ENSP00000296991
SNX3	ENST00000368979.6	c.245A>G	p.Glu82Gly	missense_variant, NMD_transcript_variant	2/5	2		ENSP00000357975

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

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 16, 2024

The c.245A>G (p.E82G) alteration is located in exon 2 (coding exon 2) of the SNX3 gene. This alteration results from a A to G substitution at nucleotide position 245, causing the glutamic acid (E) at amino acid position 82 to be replaced by a glycine (G). 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	0.66
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.35	T;.
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Uncertain	0.098	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Benign	-0.55	T
MutationAssessor	Uncertain	2.3	M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-6.1	D;D
REVEL	Uncertain	0.55
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.031	D;T
Polyphen		0.99	D;.
Vest4		0.84
MutPred		0.53		Loss of ubiquitination at K86 (P = 0.0355);.;
MVP		0.93
MPC		2.4
ClinPred		0.99	D
GERP RS		6.1
Varity_R		0.95
gMVP		0.79

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: chr6-108544167;