6-157909983-T-C

Variant names:

• chr6-157909983-T-C
• NM_016224.5:c.907T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016224.5(SNX9):​c.907T>C​(p.Ser303Pro) variant causes a missense change. 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: 4.57
• 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.907T>C	p.Ser303Pro	missense	Exon 9 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.907T>C	p.Ser303Pro	missense	Exon 9 of 18	ENSP00000376024.3	Q9Y5X1
	SNX9	ENST00000971713.1		c.997T>C	p.Ser333Pro	missense	Exon 10 of 20	ENSP00000641772.1
	SNX9	ENST00000681534.1		c.907T>C	p.Ser303Pro	missense	Exon 9 of 18	ENSP00000505127.1	A0A7P0T8C7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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	0.21
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.074	T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-1.1	N
PhyloP100		4.6
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.20
Sift	Benign	0.46	T
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.61
MutPred		0.61		Loss of phosphorylation at S303 (P = 0.1721)
MVP		0.56
MPC		1.8
ClinPred		0.75	D
GERP RS		4.4
Varity_R		0.23
gMVP		0.76
Mutation Taster		=61/39	polymorphism

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

Other links and lift over

hg19: chr6-158331015;