rs684340

Positions:

• chr6-157748231-G-A
• chr6-157748231-G-C

Variant summary

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

The ENST00000614703.4(SNX9):​c.-205-18154G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 152,132 control chromosomes in the GnomAD database, including 49,472 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 0.80 (49472 hom., cov: 32)
• Consequence: SNX9 ENST00000614703.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX9	ENST00000614703.4	c.-205-18154G>A		intron_variant		4		ENSP00000482920
SNX9	ENST00000614800.4	c.-205-18154G>A		intron_variant		4		ENSP00000479382

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121791 AN: 152014 Hom.: 49414 Cov.: 32

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.790

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.814

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.737

Gnomad OTH AF: 0.762

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

GnomAD4 genome AF: 0.801 AC: 121905 AN: 152132 Hom.: 49472 Cov.: 32 AF XY: 0.801 AC XY: 59584 AN XY: 74346

Gnomad4 AFR AF: 0.941

Gnomad4 AMR AF: 0.820

Gnomad4 ASJ AF: 0.741

Gnomad4 EAS AF: 0.687

Gnomad4 SAS AF: 0.814

Gnomad4 FIN AF: 0.722

Gnomad4 NFE AF: 0.737

Gnomad4 OTH AF: 0.762

Alfa AF: 0.761 Hom.: 5553

Bravo AF: 0.814

Asia WGS AF: 0.783 AC: 2716 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.29
DANN	Benign	0.39

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs684340; hg19: chr6-158169263;