Variant chr16-50673591-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_182854.4(SNX20):c.766C>T(p.Arg256Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000696 in 1,436,732 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000070 ( 0 hom. )

Consequence

SNX20
NM_182854.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.716

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.057897836).

BP6

Variant 16-50673591-G-A is Benign according to our data. Variant chr16-50673591-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3321293.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SNX20	NM_182854.4 linkuse as main transcript	c.766C>T	p.Arg256Cys	missense_variant	4/4	ENST00000330943.9
SNX20	NM_001144972.2 linkuse as main transcript	c.282+2179C>T		intron_variant
SNX20	NM_153337.3 linkuse as main transcript	c.282+2179C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX20	ENST00000330943.9 linkuse as main transcript	c.766C>T	p.Arg256Cys	missense_variant	4/4	1	NM_182854.4	P1	Q7Z614-1
SNX20	ENST00000423026.6 linkuse as main transcript	c.282+2179C>T		intron_variant		1			Q7Z614-4
SNX20	ENST00000568993.5 linkuse as main transcript	c.282+2179C>T		intron_variant, NMD_transcript_variant		1			Q7Z614-3
SNX20	ENST00000300590.7 linkuse as main transcript	c.282+2179C>T		intron_variant		2			Q7Z614-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000185

AC:

AN:

216040

Hom.:

AF XY:

0.0000166

AC XY:

AN XY:

120546

show subpopulations

Gnomad AFR exome

AF:

0.0000879

Gnomad AMR exome

AF:

0.0000952

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000696

AC:

AN:

1436732

Hom.:

Cov.:

AF XY:

0.00000280

AC XY:

AN XY:

714686

show subpopulations

Gnomad4 AFR exome

AF:

0.0000319

Gnomad4 AMR exome

AF:

0.0000704

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:

0.00000543

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 21, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0061

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.72

M_CAP

Benign

0.012

MetaRNN

Benign

0.058

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.97

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.43

PROVEAN

Benign

0.40

REVEL

Benign

0.14

Sift

Benign

0.23

Sift4G

Benign

0.19

Polyphen

0.0020

Vest4

0.070

MutPred

0.37

Loss of MoRF binding (P = 0.006);

MVP

0.25

MPC

0.67

ClinPred

0.043

GERP RS

-2.7

Varity_R

0.055

gMVP

0.14

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