7-2255077-C-T

Variant names:

• chr7-2255077-C-T
• rs144465573
• NM_013321.4:c.1377G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_013321.4(SNX8):​c.1377G>A​(p.Glu459Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00611 in 1,575,164 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0062 (41 hom.)
• Consequence: SNX8 NM_013321.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.59
• 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 7-2255077-C-T is Benign according to our data. Variant chr7-2255077-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2657228.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.59 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.1377G>A	p.Glu459Glu	synonymous	Exon 11 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.1377G>A	p.Glu459Glu	synonymous	Exon 11 of 11	ENSP00000222990.3	Q9Y5X2
	SNX8	ENST00000926983.1		c.1374G>A	p.Glu458Glu	synonymous	Exon 11 of 11	ENSP00000597042.1
	SNX8	ENST00000878404.1		c.1368G>A	p.Glu456Glu	synonymous	Exon 11 of 11	ENSP00000548463.1

Frequencies

GnomAD3 genomes AF: 0.00537 AC: 818 AN: 152258 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00149

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00255

Gnomad ASJ AF: 0.00807

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0183

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00707

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00574 AC: 1095 AN: 190666 AF XY: 0.00556

Gnomad AFR exome AF: 0.00143

Gnomad AMR exome AF: 0.00165

Gnomad ASJ exome AF: 0.0102

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0221

Gnomad NFE exome AF: 0.00661

Gnomad OTH exome AF: 0.00564

GnomAD4 exome AF: 0.00619 AC: 8802 AN: 1422788 Hom.: 41 Cov.: 30 AF XY: 0.00602 AC XY: 4238 AN XY: 704188

African (AFR) AF: 0.00132 AC: 43 AN: 32576

American (AMR) AF: 0.00227 AC: 89 AN: 39230

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 263 AN: 25406

East Asian (EAS) AF: 0.00 AC: 0 AN: 37468

South Asian (SAS) AF: 0.000284 AC: 23 AN: 80900

European-Finnish (FIN) AF: 0.0233 AC: 1160 AN: 49814

Middle Eastern (MID) AF: 0.00280 AC: 16 AN: 5706

European-Non Finnish (NFE) AF: 0.00628 AC: 6863 AN: 1092796

Other (OTH) AF: 0.00586 AC: 345 AN: 58892

GnomAD4 genome AF: 0.00537 AC: 818 AN: 152376 Hom.: 2 Cov.: 33 AF XY: 0.00538 AC XY: 401 AN XY: 74510

African (AFR) AF: 0.00149 AC: 62 AN: 41602

American (AMR) AF: 0.00255 AC: 39 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00807 AC: 28 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.0183 AC: 194 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00707 AC: 481 AN: 68022

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.00598 Hom.: 4

Bravo AF: 0.00420

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely 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	-0.56
CADD	Benign	6.7
DANN	Benign	0.92
PhyloP100		1.6
Mutation Taster		=99/1	polymorphism

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: rs144465573; hg19: chr7-2294712;