rs2273448

chr20-17951566-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_014426.4(SNX5):c.543G>A(p.Glu181=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,608,268 control chromosomes in the GnomAD database, including 74,015 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 0.26 (5730 hom., cov: 33)
  • Exomes 𝑓: 0.30 (68285 hom.)
• Consequence: SNX5 NM_014426.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.466

Genes affected

SNX5 (HGNC:14969): (sorting nexin 5) 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 functions in endosomal sorting, the phosphoinositide-signaling pathway, and macropinocytosis. This gene may play a role in the tumorigenesis of papillary thyroid carcinoma. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=0.466 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX5	NM_014426.4	c.543G>A	p.Glu181=	synonymous_variant	6/13	ENST00000377759.9
SNX5	NM_152227.3	c.543G>A	p.Glu181=	synonymous_variant	7/14
SNX5	NM_001282454.2	c.228G>A	p.Glu76=	synonymous_variant	6/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX5	ENST00000377759.9	c.543G>A	p.Glu181=	synonymous_variant	6/13	1	NM_014426.4	P1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39955 AN: 151976 Hom.: 5730 Cov.: 33

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.337

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.251

GnomAD3 exomes AF: 0.310 AC: 77796 AN: 251188 Hom.: 12914 AF XY: 0.318 AC XY: 43160 AN XY: 135766

Gnomad AFR exome AF: 0.153

Gnomad AMR exome AF: 0.229

Gnomad ASJ exome AF: 0.332

Gnomad EAS exome AF: 0.448

Gnomad SAS exome AF: 0.425

Gnomad FIN exome AF: 0.347

Gnomad NFE exome AF: 0.296

Gnomad OTH exome AF: 0.287

GnomAD4 exome AF: 0.301 AC: 437998 AN: 1456174 Hom.: 68285 Cov.: 31 AF XY: 0.305 AC XY: 220850 AN XY: 724606

Gnomad4 AFR exome AF: 0.148

Gnomad4 AMR exome AF: 0.231

Gnomad4 ASJ exome AF: 0.336

Gnomad4 EAS exome AF: 0.401

Gnomad4 SAS exome AF: 0.417

Gnomad4 FIN exome AF: 0.345

Gnomad4 NFE exome AF: 0.293

Gnomad4 OTH exome AF: 0.299

GnomAD4 genome AF: 0.263 AC: 39958 AN: 152094 Hom.: 5730 Cov.: 33 AF XY: 0.270 AC XY: 20078 AN XY: 74328

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.432

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.250

Alfa AF: 0.274 Hom.: 3535

Bravo AF: 0.247

Asia WGS AF: 0.412 AC: 1434 AN: 3478

EpiCase AF: 0.280

EpiControl AF: 0.278

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	9.4
Dann	Benign	0.56

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: rs2273448; hg19: chr20-17932210; COSMIC: COSV66697938; COSMIC: COSV66697938;