2-27373979-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_014748.4(SNX17):c.432+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00512 in 1,613,062 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0053 (29 hom.)
• Consequence: SNX17 NM_014748.4 splice_region, intron
• Scores: Splicing: ADA: 0.00003185
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.459

Genes affected

SNX17 (HGNC:14979): (sorting nexin 17) This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. This protein does not contain a coiled coil region, like some family members, but contains a B41 domain. This protein interacts with the cytoplasmic domain of P-selectin, and may function in the intracellular trafficking of P-selectin. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2012]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-27373979-G-A is Benign according to our data. Variant chr2-27373979-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2650767.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX17	NM_014748.4	c.432+8G>A		splice_region_variant, intron_variant		ENST00000233575.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX17	ENST00000233575.7	c.432+8G>A		splice_region_variant, intron_variant		1	NM_014748.4	P1

Frequencies

GnomAD3 genomes AF: 0.00328 AC: 499 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000844

Gnomad AMI AF: 0.00549

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00330

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00572

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.00362 AC: 909 AN: 251388 Hom.: 4 AF XY: 0.00373 AC XY: 507 AN XY: 135892

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.000926

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.00320

Gnomad FIN exome AF: 0.00347

Gnomad NFE exome AF: 0.00585

Gnomad OTH exome AF: 0.00293

GnomAD4 exome AF: 0.00531 AC: 7759 AN: 1460754 Hom.: 29 Cov.: 31 AF XY: 0.00527 AC XY: 3829 AN XY: 726764

Gnomad4 AFR exome AF: 0.00108

Gnomad4 AMR exome AF: 0.000961

Gnomad4 ASJ exome AF: 0.000306

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.00325

Gnomad4 FIN exome AF: 0.00300

Gnomad4 NFE exome AF: 0.00632

Gnomad4 OTH exome AF: 0.00333

GnomAD4 genome AF: 0.00328 AC: 499 AN: 152308 Hom.: 0 Cov.: 32 AF XY: 0.00282 AC XY: 210 AN XY: 74478

Gnomad4 AFR AF: 0.000842

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.00330

Gnomad4 NFE AF: 0.00572

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.00416 Hom.: 0

Bravo AF: 0.00313

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

SNX17: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.36
Dann	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000032
dbscSNV1_RF	Benign	0.0020
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: rs147116539; hg19: chr2-27596846;