Variant 16-50673503-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_182854.4(SNX20):c.854T>C(p.Val285Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000549 in 1,457,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

SNX20
NM_182854.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.72

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:

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=0.048743606).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SNX20	NM_182854.4 linkuse as main transcript	c.854T>C	p.Val285Ala	missense_variant	4/4	ENST00000330943.9
SNX20	NM_001144972.2 linkuse as main transcript	c.282+2267T>C		intron_variant
SNX20	NM_153337.3 linkuse as main transcript	c.282+2267T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX20	ENST00000330943.9 linkuse as main transcript	c.854T>C	p.Val285Ala	missense_variant	4/4	1	NM_182854.4	P1	Q7Z614-1
SNX20	ENST00000423026.6 linkuse as main transcript	c.282+2267T>C		intron_variant		1			Q7Z614-4
SNX20	ENST00000568993.5 linkuse as main transcript	c.282+2267T>C		intron_variant, NMD_transcript_variant		1			Q7Z614-3
SNX20	ENST00000300590.7 linkuse as main transcript	c.282+2267T>C		intron_variant		2			Q7Z614-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000123

AC:

AN:

243430

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

132580

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000273

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000549

AC:

AN:

1457440

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

725042

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

ExAC

AF:

0.00000824

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

Jan 10, 2023

The c.854T>C (p.V285A) alteration is located in exon 4 (coding exon 3) of the SNX20 gene. This alteration results from a T to C substitution at nucleotide position 854, causing the valine (V) at amino acid position 285 to be replaced by an alanine (A). 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

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.0042

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.53

M_CAP

Benign

0.0034

MetaRNN

Benign

0.049

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.62

MutationTaster

Benign

1.0

D;D;N

PrimateAI

Benign

0.46

PROVEAN

Benign

0.46

REVEL

Benign

0.051

Sift

Benign

0.74

Sift4G

Benign

0.41

Polyphen

0.0050

Vest4

0.064

MutPred

0.25

Gain of disorder (P = 0.0621);

MVP

0.18

MPC

0.60

ClinPred

0.033

GERP RS

2.3

Varity_R

0.030

gMVP

0.090

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

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