6-108260842-T-G

Position:

• chr6-108260842-T-G

Variant summary

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

The NM_003795.6(SNX3):​c.80A>C​(p.Asn27Thr) variant causes a missense change. 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 NM_003795.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.13

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.835

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX3	NM_003795.6	c.80A>C	p.Asn27Thr	missense_variant	1/4	ENST00000230085.13
SNX3	NM_001300929.2	c.80A>C	p.Asn27Thr	missense_variant	1/4
SNX3	NM_152827.4	c.80A>C	p.Asn27Thr	missense_variant	1/3
SNX3	NM_001300928.2	c.80A>C	p.Asn27Thr	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX3	ENST00000230085.13	c.80A>C	p.Asn27Thr	missense_variant	1/4	1	NM_003795.6	P1
SNX3	ENST00000426155.6	c.80A>C	p.Asn27Thr	missense_variant	1/3	1
SNX3	ENST00000349379.5	c.80A>C	p.Asn27Thr	missense_variant	1/4	2
SNX3	ENST00000368979.6	c.80A>C	p.Asn27Thr	missense_variant, NMD_transcript_variant	1/5	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Dec 22, 2023

The c.80A>C (p.N27T) alteration is located in exon 1 (coding exon 1) of the SNX3 gene. This alteration results from a A to C substitution at nucleotide position 80, causing the asparagine (N) at amino acid position 27 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	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.091	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T;.;.
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Benign	0.75	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Pathogenic	0.35	D
MetaRNN	Pathogenic	0.84	D;D;D
MetaSVM	Uncertain	0.036	D
MutationAssessor	Pathogenic	3.1	M;M;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.79	T
PROVEAN	Pathogenic	-5.3	D;D;D
REVEL	Uncertain	0.48
Sift	Uncertain	0.018	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.74
MutPred		0.46		Gain of glycosylation at S26 (P = 0.1401);Gain of glycosylation at S26 (P = 0.1401);Gain of glycosylation at S26 (P = 0.1401);
MVP		0.94
MPC		2.3
ClinPred		1.0	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.85
gMVP		0.72

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: rs1776173663; hg19: chr6-108582046;