6-108214563-A-C

Position:

• chr6-108214563-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003795.6(SNX3):​c.318T>G​(p.Asp106Glu) 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. 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: 1.97

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31814557).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX3	NM_003795.6	c.318T>G	p.Asp106Glu	missense_variant	3/4	ENST00000230085.13	NP_003786.1
SNX3	NM_001300929.2	c.252T>G	p.Asp84Glu	missense_variant	3/4		NP_001287858.1
SNX3	NM_152827.4	c.222T>G	p.Asp74Glu	missense_variant	2/3		NP_690040.1
SNX3	NM_001300928.2	c.259-2309T>G		intron_variant			NP_001287857.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX3	ENST00000230085.13	c.318T>G	p.Asp106Glu	missense_variant	3/4	1	NM_003795.6	ENSP00000230085.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Oct 06, 2021

The c.318T>G (p.D106E) alteration is located in exon 3 (coding exon 3) of the SNX3 gene. This alteration results from a T to G substitution at nucleotide position 318, causing the aspartic acid (D) at amino acid position 106 to be replaced by a glutamic acid (E). 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	0.58
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;.;.
Eigen	Benign	-0.087
Eigen_PC	Benign	-0.059
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.98	D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.32	T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.7	M;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.4	N;D;N
REVEL	Benign	0.25
Sift	Benign	0.28	T;T;T
Sift4G	Benign	0.20	T;T;T
Polyphen		0.29	B;P;.
Vest4		0.34
MutPred		0.34		Gain of disorder (P = 0.1789);.;.;
MVP		0.90
MPC		2.1
ClinPred		0.95	D
GERP RS		0.50
Varity_R		0.58
gMVP		0.55

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: chr6-108535767;