chr6-108260899-G-C

Position:

• chr6-108260899-G-C

Variant summary

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

The NM_003795.6(SNX3):​c.23C>G​(p.Thr8Ser) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SNX3 NM_003795.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.96

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=0.37885997).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX3	NM_003795.6	c.23C>G	p.Thr8Ser	missense_variant	1/4	ENST00000230085.13
SNX3	NM_001300929.2	c.23C>G	p.Thr8Ser	missense_variant	1/4
SNX3	NM_152827.4	c.23C>G	p.Thr8Ser	missense_variant	1/3
SNX3	NM_001300928.2	c.23C>G	p.Thr8Ser	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX3	ENST00000230085.13	c.23C>G	p.Thr8Ser	missense_variant	1/4	1	NM_003795.6	P1
SNX3	ENST00000426155.6	c.23C>G	p.Thr8Ser	missense_variant	1/3	1
SNX3	ENST00000349379.5	c.23C>G	p.Thr8Ser	missense_variant	1/4	2
SNX3	ENST00000368979.6	c.23C>G	p.Thr8Ser	missense_variant, NMD_transcript_variant	1/5	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

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

Jul 26, 2022

The c.23C>G (p.T8S) alteration is located in exon 1 (coding exon 1) of the SNX3 gene. This alteration results from a C to G substitution at nucleotide position 23, causing the threonine (T) at amino acid position 8 to be replaced by a serine (S). 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	0.67
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;.;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.93	D;D;D
M_CAP	Pathogenic	0.29	D
MetaRNN	Benign	0.38	T;T;T
MetaSVM	Benign	-0.37	T
MutationAssessor	Pathogenic	3.0	M;M;M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-2.2	N;N;N
REVEL	Benign	0.28
Sift	Benign	0.051	T;D;D
Sift4G	Benign	0.18	T;T;T
Polyphen		0.34	B;B;.
Vest4		0.30
MutPred		0.35		Gain of disorder (P = 0.0898);Gain of disorder (P = 0.0898);Gain of disorder (P = 0.0898);
MVP		0.79
MPC		1.1
ClinPred		0.99	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.53
gMVP		0.38

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: chr6-108582103;