rs6596

Positions:

• chr16-50675812-G-A
• chr16-50675812-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_182854.4(SNX20):​c.240C>T​(p.Ile80=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,613,286 control chromosomes in the GnomAD database, including 19,752 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 0.11 (1241 hom., cov: 32)
  • Exomes 𝑓: 0.15 (18511 hom.)
• Consequence: SNX20 NM_182854.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280

Genes affected

SNX20 (HGNC:30390): (sorting nexin 20) SNX20 interacts with the cytoplasmic domain of PSGL1 (SELPLG; MIM 600738) and cycles PSGL1 into endosomes.[supplied by OMIM, Feb 2010]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP7: Synonymous conserved (PhyloP=-0.028 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.167 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX20	NM_182854.4	c.240C>T	p.Ile80=	synonymous_variant	3/4	ENST00000330943.9	NP_878274.1
SNX20	NM_153337.3	c.240C>T	p.Ile80=	synonymous_variant	3/4		NP_699168.1
SNX20	NM_001144972.2	c.240C>T	p.Ile80=	synonymous_variant	3/4		NP_001138444.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX20	ENST00000330943.9	c.240C>T	p.Ile80=	synonymous_variant	3/4	1	NM_182854.4	ENSP00000332062	P1
SNX20	ENST00000423026.6	c.240C>T	p.Ile80=	synonymous_variant	3/4	1		ENSP00000388875
SNX20	ENST00000568993.5	c.240C>T	p.Ile80=	synonymous_variant, NMD_transcript_variant	3/5	1		ENSP00000454863
SNX20	ENST00000300590.7	c.240C>T	p.Ile80=	synonymous_variant	3/4	2		ENSP00000300590

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16367 AN: 152110 Hom.: 1242 Cov.: 32

Gnomad AFR AF: 0.0305

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.0577

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.140

GnomAD3 exomes AF: 0.106 AC: 26480 AN: 250486 Hom.: 2114 AF XY: 0.108 AC XY: 14566 AN XY: 135408

Gnomad AFR exome AF: 0.0261

Gnomad AMR exome AF: 0.0776

Gnomad ASJ exome AF: 0.146

Gnomad EAS exome AF: 0.000219

Gnomad SAS exome AF: 0.0287

Gnomad FIN exome AF: 0.0613

Gnomad NFE exome AF: 0.167

Gnomad OTH exome AF: 0.124

GnomAD4 exome AF: 0.147 AC: 215491 AN: 1461058 Hom.: 18511 Cov.: 32 AF XY: 0.145 AC XY: 105129 AN XY: 726852

Gnomad4 AFR exome AF: 0.0250

Gnomad4 AMR exome AF: 0.0809

Gnomad4 ASJ exome AF: 0.146

Gnomad4 EAS exome AF: 0.000303

Gnomad4 SAS exome AF: 0.0304

Gnomad4 FIN exome AF: 0.0627

Gnomad4 NFE exome AF: 0.173

Gnomad4 OTH exome AF: 0.129

GnomAD4 genome AF: 0.107 AC: 16364 AN: 152228 Hom.: 1241 Cov.: 32 AF XY: 0.102 AC XY: 7581 AN XY: 74432

Gnomad4 AFR AF: 0.0304

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0230

Gnomad4 FIN AF: 0.0577

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.139

Alfa AF: 0.152 Hom.: 2551

Bravo AF: 0.110

Asia WGS AF: 0.0160 AC: 57 AN: 3478

EpiCase AF: 0.178

EpiControl AF: 0.171

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	5.8
DANN	Benign	0.84

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: rs6596; hg19: chr16-50709723; COSMIC: COSV56059296; COSMIC: COSV56059296;