chr6-157867616-A-T

Variant names:

• chr6-157867616-A-T
• NM_016224.5:c.82A>T

Variant summary

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

The NM_016224.5(SNX9):​c.82A>T​(p.Ile28Phe) 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: SNX9 NM_016224.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.04

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39881074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX9	NM_016224.5	c.82A>T	p.Ile28Phe	missense_variant	Exon 2 of 18	ENST00000392185.8	NP_057308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNX9	ENST00000392185.8	c.82A>T	p.Ile28Phe	missense_variant	Exon 2 of 18	1	NM_016224.5	ENSP00000376024.3

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

Jan 10, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.82A>T (p.I28F) alteration is located in exon 2 (coding exon 2) of the SNX9 gene. This alteration results from a A to T substitution at nucleotide position 82, causing the isoleucine (I) at amino acid position 28 to be replaced by a phenylalanine (F). 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	0.72
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;.;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.97	D;D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	.;.;L
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-2.4	.;.;N
REVEL	Benign	0.25
Sift	Uncertain	0.0040	.;.;D
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		0.97	.;.;D
Vest4		0.85
MutPred		0.49		.;.;Gain of catalytic residue at I28 (P = 0.0193);
MVP		0.31
MPC		0.34
ClinPred		0.90	D
GERP RS		5.4
Varity_R		0.24
gMVP		0.88

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: chr6-158288648;