chr7-2256865-C-A

Variant names:

• chr7-2256865-C-A
• rs115870022
• NM_013321.4:c.1284+9G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_013321.4(SNX8):​c.1284+9G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00471 in 1,607,446 control chromosomes in the GnomAD database, including 319 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (143 hom., cov: 34)
  • Exomes 𝑓: 0.0027 (176 hom.)
• Consequence: SNX8 NM_013321.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.57
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-2256865-C-A is Benign according to our data. Variant chr7-2256865-C-A is described in ClinVar as Benign. ClinVar VariationId is 768130.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0825 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.1284+9G>T		intron	N/A	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.1284+9G>T		intron	N/A	ENSP00000222990.3	Q9Y5X2
	SNX8	ENST00000926983.1		c.1281+9G>T		intron	N/A	ENSP00000597042.1
	SNX8	ENST00000878404.1		c.1275+9G>T		intron	N/A	ENSP00000548463.1

Frequencies

GnomAD3 genomes AF: 0.0244 AC: 3712 AN: 152180 Hom.: 143 Cov.: 34

Gnomad AFR AF: 0.0849

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0167

GnomAD2 exomes AF: 0.00625 AC: 1534 AN: 245526 AF XY: 0.00421

Gnomad AFR exome AF: 0.0858

Gnomad AMR exome AF: 0.00370

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000154

Gnomad OTH exome AF: 0.00352

GnomAD4 exome AF: 0.00265 AC: 3861 AN: 1455148 Hom.: 176 Cov.: 38 AF XY: 0.00223 AC XY: 1615 AN XY: 723140

African (AFR) AF: 0.0953 AC: 3177 AN: 33348

American (AMR) AF: 0.00420 AC: 186 AN: 44288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25784

East Asian (EAS) AF: 0.00 AC: 0 AN: 39530

South Asian (SAS) AF: 0.000187 AC: 16 AN: 85640

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52612

Middle Eastern (MID) AF: 0.00632 AC: 35 AN: 5534

European-Non Finnish (NFE) AF: 0.0000983 AC: 109 AN: 1108334

Other (OTH) AF: 0.00561 AC: 337 AN: 60078

GnomAD4 genome AF: 0.0244 AC: 3718 AN: 152298 Hom.: 143 Cov.: 34 AF XY: 0.0233 AC XY: 1737 AN XY: 74470

African (AFR) AF: 0.0848 AC: 3525 AN: 41554

American (AMR) AF: 0.00915 AC: 140 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68020

Other (OTH) AF: 0.0165 AC: 35 AN: 2116

Alfa AF: 0.0123 Hom.: 37

Bravo AF: 0.0279

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.86
DANN	Benign	0.57
PhyloP100		-1.6
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: rs115870022; hg19: chr7-2296500; COSMIC: COSV56126525; COSMIC: COSV56126525;