chr7-2258592-C-T

Position:

• chr7-2258592-C-T

Variant summary

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

The NM_013321.4(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 NM_013321.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.90

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]

SNX8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX8	NM_013321.4	c.916-789G>A		intron_variant		ENST00000222990.8	NP_037453.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX8	ENST00000222990.8	c.916-789G>A		intron_variant		1	NM_013321.4	ENSP00000222990.3
SNX8	ENST00000479689.1	n.423-789G>A		intron_variant		2

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

Gnomad4 AFR AF: 0.0731

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.295

Alfa AF: 0.343 Hom.: 12773

Bravo AF: 0.276

Asia WGS AF: 0.403 AC: 1400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.55
DANN	Benign	0.63

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: rs2398668; hg19: chr7-2298227; COSMIC: COSV56130485; COSMIC: COSV56130485;