16-50675881-C-T

Variant names:

• chr16-50675881-C-T
• rs35435054
• NM_182854.4:c.171G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_182854.4(SNX20):​c.171G>A​(p.Thr57Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00267 in 1,612,116 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (59 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (47 hom.)
• Consequence: SNX20 NM_182854.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.24
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 16-50675881-C-T is Benign according to our data. Variant chr16-50675881-C-T is described in ClinVar as Benign. ClinVar VariationId is 777015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.24 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0147 (2235/152270) while in subpopulation AFR AF = 0.051 (2121/41558). AF 95% confidence interval is 0.0492. There are 59 homozygotes in GnomAd4. There are 1024 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 59 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182854.4. 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
	SNX20	NM_182854.4	MANE Select	c.171G>A	p.Thr57Thr	synonymous	Exon 3 of 4	NP_878274.1	Q7Z614-1
	SNX20	NM_153337.3		c.171G>A	p.Thr57Thr	synonymous	Exon 3 of 4	NP_699168.1	Q7Z614-3
	SNX20	NM_001144972.2		c.171G>A	p.Thr57Thr	synonymous	Exon 3 of 4	NP_001138444.1	Q7Z614-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNX20	ENST00000330943.9	TSL:1 MANE Select	c.171G>A	p.Thr57Thr	synonymous	Exon 3 of 4	ENSP00000332062.4	Q7Z614-1
	SNX20	ENST00000423026.6	TSL:1	c.171G>A	p.Thr57Thr	synonymous	Exon 3 of 4	ENSP00000388875.2	Q7Z614-4
	SNX20	ENST00000568993.5	TSL:1	n.171G>A		non_coding_transcript_exon	Exon 3 of 5	ENSP00000454863.1	Q7Z614-3

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2224 AN: 152152 Hom.: 59 Cov.: 32

Gnomad AFR AF: 0.0509

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0144

GnomAD2 exomes AF: 0.00364 AC: 906 AN: 249224 AF XY: 0.00263

Gnomad AFR exome AF: 0.0508

Gnomad AMR exome AF: 0.00170

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.00142 AC: 2066 AN: 1459846 Hom.: 47 Cov.: 31 AF XY: 0.00123 AC XY: 891 AN XY: 726316

African (AFR) AF: 0.0513 AC: 1709 AN: 33312

American (AMR) AF: 0.00225 AC: 99 AN: 44014

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53304

Middle Eastern (MID) AF: 0.00244 AC: 14 AN: 5746

European-Non Finnish (NFE) AF: 0.0000558 AC: 62 AN: 1111360

Other (OTH) AF: 0.00284 AC: 171 AN: 60292

GnomAD4 genome AF: 0.0147 AC: 2235 AN: 152270 Hom.: 59 Cov.: 32 AF XY: 0.0138 AC XY: 1024 AN XY: 74456

African (AFR) AF: 0.0510 AC: 2121 AN: 41558

American (AMR) AF: 0.00445 AC: 68 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68026

Other (OTH) AF: 0.0142 AC: 30 AN: 2112

Alfa AF: 0.00694 Hom.: 14

Bravo AF: 0.0167

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0000546

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	1.2
DANN	Benign	0.83
PhyloP100		-4.2
Mutation Taster		=100/0	polymorphism

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: rs35435054; hg19: chr16-50709792;