rs9355434

chr6-157925231-A-Gchr6-157925231-A-T

Variant summary

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

The NM_016224.5(SNX9):c.1081-1880A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,132 control chromosomes in the GnomAD database, including 3,625 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 0.22 (3625 hom., cov: 32)
• Consequence: SNX9 NM_016224.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX9	NM_016224.5	c.1081-1880A>G		intron_variant		ENST00000392185.8
SNX9	XM_011535886.4	c.799-1880A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX9	ENST00000392185.8	c.1081-1880A>G		intron_variant		1	NM_016224.5	P1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32866 AN: 152014 Hom.: 3613 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.216 AC: 32916 AN: 152132 Hom.: 3625 Cov.: 32 AF XY: 0.215 AC XY: 16022 AN XY: 74356

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.214

Alfa AF: 0.214 Hom.: 453

Bravo AF: 0.210

Asia WGS AF: 0.165 AC: 572 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.84
Dann	Benign	0.61

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: rs9355434; hg19: chr6-158346263;