20-17951566-C-T

Variant names:

• chr20-17951566-C-T
• rs2273448
• NM_014426.4:c.543G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_014426.4(SNX5):​c.543G>A​(p.Glu181Glu) 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
• Publications: 18 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 -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX5	NM_014426.4	MANE Select	c.543G>A	p.Glu181Glu	synonymous	Exon 6 of 13	NP_055241.1	Q9Y5X3-1
	SNX5	NM_152227.3		c.543G>A	p.Glu181Glu	synonymous	Exon 7 of 14	NP_689413.1	Q9Y5X3-1
	SNX5	NM_001282454.2		c.228G>A	p.Glu76Glu	synonymous	Exon 6 of 13	NP_001269383.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX5	ENST00000377759.9	TSL:1 MANE Select	c.543G>A	p.Glu181Glu	synonymous	Exon 6 of 13	ENSP00000366988.3	Q9Y5X3-1
	SNX5	ENST00000377768.7	TSL:1	c.543G>A	p.Glu181Glu	synonymous	Exon 7 of 14	ENSP00000366998.3	Q9Y5X3-1
	SNX5	ENST00000490175.5	TSL:1	n.593G>A		non_coding_transcript_exon	Exon 6 of 13

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

GnomAD2 exomes AF: 0.310 AC: 77796 AN: 251188 AF XY: 0.318

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 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

African (AFR) AF: 0.148 AC: 4953 AN: 33392

American (AMR) AF: 0.231 AC: 10335 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 8753 AN: 26084

East Asian (EAS) AF: 0.401 AC: 15887 AN: 39614

South Asian (SAS) AF: 0.417 AC: 35836 AN: 86014

European-Finnish (FIN) AF: 0.345 AC: 18421 AN: 53372

Middle Eastern (MID) AF: 0.214 AC: 1077 AN: 5038

European-Non Finnish (NFE) AF: 0.293 AC: 324772 AN: 1107862

Other (OTH) AF: 0.299 AC: 17964 AN: 60130

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

African (AFR) AF: 0.151 AC: 6255 AN: 41502

American (AMR) AF: 0.257 AC: 3926 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1136 AN: 3468

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

South Asian (SAS) AF: 0.432 AC: 2087 AN: 4828

European-Finnish (FIN) AF: 0.344 AC: 3624 AN: 10546

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

European-Non Finnish (NFE) AF: 0.291 AC: 19772 AN: 67974

Other (OTH) AF: 0.250 AC: 529 AN: 2112

Alfa AF: 0.272 Hom.: 3937

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	9.4
DANN	Benign	0.56
PhyloP100		0.47
PromoterAI		-0.024	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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