chr6-157921645-A-T

Variant names:

• chr6-157921645-A-T
• NM_016224.5:c.1064A>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016224.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX9	NM_016224.5	MANE Select	c.1064A>T	p.Asn355Ile	missense	Exon 10 of 18	NP_057308.1	Q9Y5X1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX9	ENST00000392185.8	TSL:1 MANE Select	c.1064A>T	p.Asn355Ile	missense	Exon 10 of 18	ENSP00000376024.3	Q9Y5X1
	SNX9	ENST00000971713.1		c.1154A>T	p.Asn385Ile	missense	Exon 11 of 20	ENSP00000641772.1
	SNX9	ENST00000681534.1		c.1064A>T	p.Asn355Ile	missense	Exon 10 of 18	ENSP00000505127.1	A0A7P0T8C7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		1.0
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
Mutation Taster		=67/33	polymorphism

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

Other links and lift over

hg19: chr6-158342677;