6-157868514-G-C

Position:

• chr6-157868514-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000392185.8(SNX9):​c.99+881G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0324 in 152,206 control chromosomes in the GnomAD database, including 211 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.032 (211 hom., cov: 32)
• Consequence: SNX9 ENST00000392185.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.511

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX9	NM_016224.5	c.99+881G>C		intron_variant		ENST00000392185.8	NP_057308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX9	ENST00000392185.8	c.99+881G>C		intron_variant		1	NM_016224.5	ENSP00000376024	P1

Frequencies

GnomAD3 genomes AF: 0.0324 AC: 4926 AN: 152088 Hom.: 210 Cov.: 32

Gnomad AFR AF: 0.0937

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0170

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00405

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00863

Gnomad OTH AF: 0.0239

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0324 AC: 4932 AN: 152206 Hom.: 211 Cov.: 32 AF XY: 0.0311 AC XY: 2317 AN XY: 74432

Gnomad4 AFR AF: 0.0936

Gnomad4 AMR AF: 0.0169

Gnomad4 ASJ AF: 0.0256

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00405

Gnomad4 NFE AF: 0.00862

Gnomad4 OTH AF: 0.0237

Alfa AF: 0.0218 Hom.: 15

Bravo AF: 0.0361

Asia WGS AF: 0.00693 AC: 24 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.8
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97

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

LitVar

Other links and lift over

dbSNP: rs6937267; hg19: chr6-158289546;