6-157921645-A-T

Position:

• chr6-157921645-A-T

Variant summary

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

The NM_016224.5(SNX9):​c.1064A>T​(p.Asn355Ile) variant causes a missense change involving the alteration of a non-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: 32)
• Consequence: SNX9 NM_016224.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.04

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.1064A>T	p.Asn355Ile	missense_variant	10/18	ENST00000392185.8
SNX9	XM_011535886.4	c.782A>T	p.Asn261Ile	missense_variant	7/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX9	ENST00000392185.8	c.1064A>T	p.Asn355Ile	missense_variant	10/18	1	NM_016224.5	P1

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

Jun 07, 2023

The c.1064A>T (p.N355I) alteration is located in exon 10 (coding exon 10) of the SNX9 gene. This alteration results from a A to T substitution at nucleotide position 1064, causing the asparagine (N) at amino acid position 355 to be replaced by an isoleucine (I). 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	0.20
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.40	T
Eigen	Benign	-0.094
Eigen_PC	Benign	-0.094
FATHMM_MKL	Benign	0.60	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.42	N
MutationTaster	Benign	0.94	N;N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.11
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.014	D
Polyphen		0.85	P
Vest4		0.65
MutPred		0.56		Loss of disorder (P = 0.0785);
MVP		0.38
MPC		1.5
ClinPred		0.50	T
GERP RS		1.8
Varity_R		0.20
gMVP		0.66

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: chr6-158342677;