20-17955178-T-C

Variant names:

• chr20-17955178-T-C
• rs10485575
• NM_014426.4:c.267+187A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014426.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX5	NM_014426.4	MANE Select	c.267+187A>G		intron	N/A	NP_055241.1
	SNX5	NM_152227.3		c.267+187A>G		intron	N/A	NP_689413.1
	SNX5	NM_001282454.2		c.-49+187A>G		intron	N/A	NP_001269383.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX5	ENST00000377759.9	TSL:1 MANE Select	c.267+187A>G		intron	N/A	ENSP00000366988.3
	SNX5	ENST00000377768.7	TSL:1	c.267+187A>G		intron	N/A	ENSP00000366998.3
	SNX5	ENST00000490175.5	TSL:1	n.317+187A>G		intron	N/A

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

African (AFR) AF: 0.151 AC: 6259 AN: 41530

American (AMR) AF: 0.257 AC: 3924 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1137 AN: 3472

East Asian (EAS) AF: 0.438 AC: 2266 AN: 5170

South Asian (SAS) AF: 0.432 AC: 2083 AN: 4822

European-Finnish (FIN) AF: 0.344 AC: 3640 AN: 10570

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19778 AN: 67980

Other (OTH) AF: 0.250 AC: 528 AN: 2112

Alfa AF: 0.274 Hom.: 2611

Bravo AF: 0.247

Asia WGS AF: 0.413 AC: 1437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.3
DANN	Benign	0.53
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10485575; hg19: chr20-17935822;