rs2286206

Variant names:

• chr7-2264351-T-C
• rs2286206
• NM_013321.4:c.729A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_013321.4(SNX8):​c.729A>G​(p.Ala243Ala) 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
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013321.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX8	NM_013321.4	MANE Select	c.729A>G	p.Ala243Ala	synonymous	Exon 6 of 11	NP_037453.1	Q9Y5X2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX8	ENST00000222990.8	TSL:1 MANE Select	c.729A>G	p.Ala243Ala	synonymous	Exon 6 of 11	ENSP00000222990.3	Q9Y5X2
	SNX8	ENST00000926983.1		c.729A>G	p.Ala243Ala	synonymous	Exon 6 of 11	ENSP00000597042.1
	SNX8	ENST00000878404.1		c.729A>G	p.Ala243Ala	synonymous	Exon 6 of 11	ENSP00000548463.1

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

GnomAD2 exomes AF: 0.912 AC: 228377 AN: 250412 AF XY: 0.916

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 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

African (AFR) AF: 0.758 AC: 25363 AN: 33478

American (AMR) AF: 0.879 AC: 39306 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.902 AC: 23578 AN: 26132

East Asian (EAS) AF: 0.805 AC: 31963 AN: 39698

South Asian (SAS) AF: 0.876 AC: 75526 AN: 86242

European-Finnish (FIN) AF: 0.958 AC: 50099 AN: 52302

Middle Eastern (MID) AF: 0.906 AC: 5222 AN: 5766

European-Non Finnish (NFE) AF: 0.967 AC: 1074566 AN: 1111806

Other (OTH) AF: 0.936 AC: 56492 AN: 60370

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

African (AFR) AF: 0.766 AC: 31779 AN: 41502

American (AMR) AF: 0.898 AC: 13737 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.902 AC: 3133 AN: 3472

East Asian (EAS) AF: 0.813 AC: 4202 AN: 5166

South Asian (SAS) AF: 0.872 AC: 4212 AN: 4830

European-Finnish (FIN) AF: 0.956 AC: 10157 AN: 10624

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.963 AC: 65505 AN: 68034

Other (OTH) AF: 0.898 AC: 1898 AN: 2114

Alfa AF: 0.930 Hom.: 45182

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.24
DANN	Benign	0.25
PhyloP100		-5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2286206; hg19: chr7-2303986; COSMIC: COSV108074820; COSMIC: COSV108074820;