rs2286206

Positions:

• chr7-2264351-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_013321.4(SNX8):​c.729A>G​(p.Ala243=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 1,612,744 control chromosomes in the GnomAD database, including 716,873 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 0.89 (61167 hom., cov: 33)
  • Exomes 𝑓: 0.95 (655706 hom.)
• Consequence: SNX8 NM_013321.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.45

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-5.45 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX8	NM_013321.4	c.729A>G	p.Ala243=	synonymous_variant	6/11	ENST00000222990.8	NP_037453.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX8	ENST00000222990.8	c.729A>G	p.Ala243=	synonymous_variant	6/11	1	NM_013321.4	ENSP00000222990	P1
SNX8	ENST00000479689.1	n.236A>G		non_coding_transcript_exon_variant	3/5	2
SNX8	ENST00000435060.5			downstream_gene_variant		5		ENSP00000392437
SNX8	ENST00000457286.5			downstream_gene_variant		3		ENSP00000406954

Frequencies

GnomAD3 genomes AF: 0.892 AC: 135683 AN: 152120 Hom.: 61119 Cov.: 33

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.898

Gnomad ASJ AF: 0.902

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.872

Gnomad FIN AF: 0.956

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.963

Gnomad OTH AF: 0.896

GnomAD3 exomes AF: 0.912 AC: 228377 AN: 250412 Hom.: 104696 AF XY: 0.916 AC XY: 124124 AN XY: 135544

Gnomad AFR exome AF: 0.764

Gnomad AMR exome AF: 0.877

Gnomad ASJ exome AF: 0.900

Gnomad EAS exome AF: 0.812

Gnomad SAS exome AF: 0.874

Gnomad FIN exome AF: 0.957

Gnomad NFE exome AF: 0.962

Gnomad OTH exome AF: 0.934

GnomAD4 exome AF: 0.946 AC: 1382115 AN: 1460506 Hom.: 655706 Cov.: 51 AF XY: 0.945 AC XY: 686580 AN XY: 726572

Gnomad4 AFR exome AF: 0.758

Gnomad4 AMR exome AF: 0.879

Gnomad4 ASJ exome AF: 0.902

Gnomad4 EAS exome AF: 0.805

Gnomad4 SAS exome AF: 0.876

Gnomad4 FIN exome AF: 0.958

Gnomad4 NFE exome AF: 0.967

Gnomad4 OTH exome AF: 0.936

GnomAD4 genome AF: 0.892 AC: 135790 AN: 152238 Hom.: 61167 Cov.: 33 AF XY: 0.890 AC XY: 66280 AN XY: 74436

Gnomad4 AFR AF: 0.766

Gnomad4 AMR AF: 0.898

Gnomad4 ASJ AF: 0.902

Gnomad4 EAS AF: 0.813

Gnomad4 SAS AF: 0.872

Gnomad4 FIN AF: 0.956

Gnomad4 NFE AF: 0.963

Gnomad4 OTH AF: 0.898

Alfa AF: 0.931 Hom.: 40212

Bravo AF: 0.883

Asia WGS AF: 0.878 AC: 3049 AN: 3478

EpiCase AF: 0.957

EpiControl AF: 0.959

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.24
DANN	Benign	0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs2286206; hg19: chr7-2303986;