15-75649551-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153271.2(SNX33):​c.449C>T​(p.Ala150Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,482 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: 0.0000027 ( 0 hom. )

Consequence

SNX33
NM_153271.2 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.92
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1264461).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SNX33NM_153271.2 linkc.449C>T p.Ala150Val missense_variant Exon 1 of 2 ENST00000308527.6 NP_695003.1 Q8WV41
SNX33NM_001318146.1 linkc.449C>T p.Ala150Val missense_variant Exon 1 of 3 NP_001305075.1 Q8WV41

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SNX33ENST00000308527.6 linkc.449C>T p.Ala150Val missense_variant Exon 1 of 2 1 NM_153271.2 ENSP00000311427.6 Q8WV41
SNX33ENST00000569152.1 linkc.-206C>T upstream_gene_variant 2 ENSP00000455436.1 H3BPR3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1460482
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
726434
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 21, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.449C>T (p.A150V) alteration is located in exon 1 (coding exon 1) of the SNX33 gene. This alteration results from a C to T substitution at nucleotide position 449, causing the alanine (A) at amino acid position 150 to be replaced by a valine (V). 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
0.074
BayesDel_addAF
Benign
-0.054
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.046
T
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.012
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Benign
0.73
T
M_CAP
Benign
0.020
T
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
0.55
N
PrimateAI
Uncertain
0.49
T
PROVEAN
Benign
-1.0
N
REVEL
Benign
0.030
Sift
Benign
0.094
T
Sift4G
Benign
0.24
T
Polyphen
0.15
B
Vest4
0.10
MutPred
0.22
Loss of disorder (P = 0.0882);
MVP
0.65
MPC
0.50
ClinPred
0.44
T
GERP RS
4.9
Varity_R
0.17
gMVP
0.51

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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.

Other links and lift over

dbSNP: rs902526510; hg19: chr15-75941892; API