7-2306480-C-T

Variant names:

• chr7-2306480-C-T
• rs10249052
• NM_013321.4:c.94+7848G>A

Variant summary

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

The NM_013321.4(SNX8):​c.94+7848G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 151,936 control chromosomes in the GnomAD database, including 10,466 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 0.36 (10466 hom., cov: 32)
• Consequence: SNX8 NM_013321.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX8	NM_013321.4	c.94+7848G>A		intron_variant	Intron 1 of 10	ENST00000222990.8	NP_037453.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNX8	ENST00000222990.8	c.94+7848G>A		intron_variant	Intron 1 of 10	1	NM_013321.4	ENSP00000222990.3

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55373 AN: 151818 Hom.: 10437 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.365 AC: 55449 AN: 151936 Hom.: 10466 Cov.: 32 AF XY: 0.368 AC XY: 27356 AN XY: 74260

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.277

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.359

Alfa AF: 0.347 Hom.: 9261

Bravo AF: 0.378

Asia WGS AF: 0.536 AC: 1860 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.89
DANN	Benign	0.60

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: rs10249052; hg19: chr7-2346115;