rs12670380

Positions:

• chr7-2323494-A-C
• chr7-2323494-A-T

Variant summary

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

The ENST00000435336.5(SNX8):​c.-66+30728T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 151,994 control chromosomes in the GnomAD database, including 6,717 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 0.29 (6717 hom., cov: 32)
• Consequence: SNX8 ENST00000435336.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.418

Genes affected

SNX8 (HGNC:14972): (sorting nexin 8) Enables identical protein binding activity and phosphatidylinositol binding activity. Involved in early endosome to Golgi transport and intracellular protein transport. Located in early endosome membrane. Colocalizes with retromer complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX8	XM_017012084.3	c.-66+30728T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX8	ENST00000435336.5	c.-66+30728T>G		intron_variant		5
SNX8	ENST00000447136.1	c.-66+13622T>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44522 AN: 151876 Hom.: 6711 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.293 AC: 44545 AN: 151994 Hom.: 6717 Cov.: 32 AF XY: 0.289 AC XY: 21467 AN XY: 74298

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.248

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.309

Alfa AF: 0.280 Hom.: 12496

Bravo AF: 0.301

Asia WGS AF: 0.221 AC: 771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.9
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12670380; hg19: chr7-2363129;