chr6-157909722-G-A

Position:

• chr6-157909722-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_016224.5(SNX9):​c.763G>A​(p.Ala255Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SNX9 NM_016224.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.48

Genes affected

SNX9 (HGNC:14973): (sorting nexin 9) This gene encodes a member of the sorting nexin family. Members of this family contain a phosphoinositide binding domain, and are involved in intracellular trafficking. The encoded protein does not contain a coiled coil region, like some family members, but does contain a SRC homology domain near its N-terminus. The encoded protein is reported to have a variety of interaction partners, including of adaptor protein 2 , dynamin, tyrosine kinase non-receptor 2, Wiskott-Aldrich syndrome-like, and ARP3 actin-related protein 3. The encoded protein is implicated in several stages of intracellular trafficking, including endocytosis, macropinocytosis, and F-actin nucleation. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX9	NM_016224.5	c.763G>A	p.Ala255Thr	missense_variant	8/18	ENST00000392185.8
SNX9	XM_011535886.4	c.481G>A	p.Ala161Thr	missense_variant	5/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX9	ENST00000392185.8	c.763G>A	p.Ala255Thr	missense_variant	8/18	1	NM_016224.5	P1

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

May 26, 2024

The c.763G>A (p.A255T) alteration is located in exon 8 (coding exon 8) of the SNX9 gene. This alteration results from a G to A substitution at nucleotide position 763, causing the alanine (A) at amino acid position 255 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	Benign	0.29
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.041	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.35	N
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.37
Sift	Benign	0.077	T
Sift4G	Benign	0.079	T
Polyphen		1.0	D
Vest4		0.66
MutPred		0.51		Gain of phosphorylation at A255 (P = 0.0279);
MVP		0.58
MPC		2.1
ClinPred		0.97	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.41
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr6-158330754;