Genetic Variant SNX33:p.Asp112Glu (chr15-75649438-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_153271.2(SNX33):c.336T>G(p.Asp112Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000079 in 1,531,910 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000082 ( 0 hom. )

Consequence

SNX33
NM_153271.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.04

Variant links:

Genes affected

SNX33 (HGNC:28468): (sorting nexin 33) The protein encoded by this gene is involved in cytoskeletal reorganization, vesicle trafficking, endocytosis, and mitosis. The encoded protein is essential for the creation of the cleavage furrow during mitosis and for completion of mitosis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

SNX33 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=0.0219976).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX33	NM_153271.2 link	c.336T>G	p.Asp112Glu	missense_variant	Exon 1 of 2	ENST00000308527.6	NP_695003.1	Q8WV41
SNX33	NM_001318146.1 link	c.336T>G	p.Asp112Glu	missense_variant	Exon 1 of 3		NP_001305075.1	Q8WV41

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNX33	ENST00000308527.6 link	c.336T>G	p.Asp112Glu	missense_variant	Exon 1 of 2	1	NM_153271.2	ENSP00000311427.6		Q8WV41

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152018

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000941

AC:

AN:

191252

Hom.:

AF XY:

0.0000594

AC XY:

AN XY:

101018

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000160

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000571

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.000223

GnomAD4 exome

AF:

0.0000819

AC:

113

AN:

1379892

Hom.:

Cov.:

AF XY:

0.0000813

AC XY:

AN XY:

676502

show subpopulations

Gnomad4 AFR exome

AF:

0.0000958

Gnomad4 AMR exome

AF:

0.000143

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000519

Gnomad4 SAS exome

AF:

0.0000136

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000888

Gnomad4 OTH exome

AF:

0.0000879

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152018

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74224

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000912

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 15, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.336T>G (p.D112E) alteration is located in exon 1 (coding exon 1) of the SNX33 gene. This alteration results from a T to G substitution at nucleotide position 336, causing the aspartic acid (D) at amino acid position 112 to be replaced by a glutamic acid (E). 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

0.089

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.0010

DANN

Benign

0.57

DEOGEN2

Benign

0.026

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.55

M_CAP

Benign

0.017

MetaRNN

Benign

0.022

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.57

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.37

REVEL

Benign

0.048

Sift

Benign

1.0

Sift4G

Benign

0.50

Polyphen

0.0

Vest4

0.15

MutPred

0.22

Loss of glycosylation at S108 (P = 0.2349);

MVP

0.42

MPC

0.40

ClinPred

0.023

GERP RS

-2.0

Varity_R

0.042

gMVP

0.22

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