7-2258592-C-T

Variant names:

• chr7-2258592-C-T
• rs2398668
• NM_013321.4:c.916-789G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000222990.8(SNX8):​c.916-789G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,076 control chromosomes in the GnomAD database, including 7,146 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 0.27 (7146 hom., cov: 32)
• Consequence: SNX8 ENST00000222990.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.90
• Publications: 18 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000222990.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX8	NM_013321.4	MANE Select	c.916-789G>A		intron	N/A	NP_037453.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX8	ENST00000222990.8	TSL:1 MANE Select	c.916-789G>A		intron	N/A	ENSP00000222990.3
	SNX8	ENST00000479689.1	TSL:2	n.423-789G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41594 AN: 151958 Hom.: 7146 Cov.: 32

Gnomad AFR AF: 0.0732

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.274 AC: 41596 AN: 152076 Hom.: 7146 Cov.: 32 AF XY: 0.272 AC XY: 20237 AN XY: 74316

African (AFR) AF: 0.0731 AC: 3034 AN: 41528

American (AMR) AF: 0.350 AC: 5355 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 907 AN: 3468

East Asian (EAS) AF: 0.514 AC: 2651 AN: 5154

South Asian (SAS) AF: 0.274 AC: 1318 AN: 4818

European-Finnish (FIN) AF: 0.252 AC: 2668 AN: 10574

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24690 AN: 67942

Other (OTH) AF: 0.295 AC: 622 AN: 2108

Alfa AF: 0.320 Hom.: 16778

Bravo AF: 0.276

Asia WGS AF: 0.403 AC: 1400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.55
DANN	Benign	0.63
PhyloP100		-2.9
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: rs2398668; hg19: chr7-2298227; COSMIC: COSV56130485; COSMIC: COSV56130485;