Variant rs2273448 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.466

Variant links:

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]

SNX5 links:

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ACMG classification

Classification made for transcript

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	Protein
SNX5	NM_014426.4 linkuse as main transcript	c.543G>A	p.Glu181=	synonymous_variant	6/13	ENST00000377759.9	NP_055241.1
SNX5	NM_152227.3 linkuse as main transcript	c.543G>A	p.Glu181=	synonymous_variant	7/14		NP_689413.1
SNX5	NM_001282454.2 linkuse as main transcript	c.228G>A	p.Glu76=	synonymous_variant	6/13		NP_001269383.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX5	ENST00000377759.9 linkuse as main transcript	c.543G>A	p.Glu181=	synonymous_variant	6/13	1	NM_014426.4	ENSP00000366988	P1	Q9Y5X3-1

Frequencies

GnomAD3 genomes

AF:

0.263

AC:

39955

AN:

151976

Hom.:

5730

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.305

AC XY:

220850

AN XY:

724606

show subpopulations

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.:

AF XY:

0.270

AC XY:

20078

AN XY:

74328

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over