Variant chr16-50669146-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000423026.6(SNX20):c.283-1105G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000339 in 1,252,504 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00035 ( 1 hom. )

Consequence

SNX20
ENST00000423026.6 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.213

Variant links:

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]

SNX20 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.011925906).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons
LOC101927272	NR_110908.1 linkuse as main transcript	n.292C>T		non_coding_transcript_exon_variant	1/3
SNX20	NM_153337.3 linkuse as main transcript	c.285G>A	p.Met95Ile	missense_variant, splice_region_variant	4/4
SNX20	NM_001144972.2 linkuse as main transcript	c.283-1105G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000570241.3 linkuse as main transcript	n.4244C>T		non_coding_transcript_exon_variant	1/3	1

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000422

AC:

AN:

151680

Hom.:

AF XY:

0.000384

AC XY:

AN XY:

80680

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00177

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000439

Gnomad FIN exome

AF:

0.000589

Gnomad NFE exome

AF:

0.000663

Gnomad OTH exome

AF:

0.000231

GnomAD4 exome

AF:

0.000348

AC:

383

AN:

1100298

Hom.:

Cov.:

AF XY:

0.000353

AC XY:

196

AN XY:

555572

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00163

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000410

Gnomad4 FIN exome

AF:

0.000407

Gnomad4 NFE exome

AF:

0.000383

Gnomad4 OTH exome

AF:

0.000270

GnomAD4 genome

AF:

0.000276

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000442

Hom.:

Bravo

AF:

0.000257

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000943

AC:

ExAC

AF:

0.000322

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.285G>A (p.M95I) alteration is located in exon 4 (coding exon 3) of the SNX20 gene. This alteration results from a G to A substitution at nucleotide position 285, causing the methionine (M) at amino acid position 95 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.62

CADD

Benign

6.3

DANN

Benign

0.91

Eigen

Benign

-0.98

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.031

M_CAP

Benign

0.0061

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

-1.6

REVEL

Benign

0.016

Sift

Benign

0.065

Sift4G

Uncertain

0.030

Polyphen

0.0010

Vest4

0.093

MutPred

0.33

Gain of ubiquitination at K97 (P = 0.077);

MVP

0.23

ClinPred

0.015

GERP RS

-0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over