rs10485575

chr20-17955178-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014426.4(SNX5):c.267+187A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 152,150 control chromosomes in the GnomAD database, including 5,739 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 (5739 hom., cov: 32)
• Consequence: SNX5 NM_014426.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• 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.267+187A>G		intron_variant		ENST00000377759.9
SNX5	NM_001282454.2	c.-49+187A>G		intron_variant
SNX5	NM_152227.3	c.267+187A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX5	ENST00000377759.9	c.267+187A>G		intron_variant		1	NM_014426.4	P1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39977 AN: 152032 Hom.: 5739 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.327

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: 0.250

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.263 AC: 39980 AN: 152150 Hom.: 5739 Cov.: 32 AF XY: 0.270 AC XY: 20098 AN XY: 74398

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.327

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: 0.278 Hom.: 2204

Bravo AF: 0.247

Asia WGS AF: 0.413 AC: 1437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	3.3
Dann	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10485575; hg19: chr20-17935822;