15-75649551-C-T

Variant names:

• chr15-75649551-C-T
• rs902526510
• NM_153271.2:c.449C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.92

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]

ACMG classification

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
SNX33	NM_153271.2	c.449C>T	p.Ala150Val	missense_variant	Exon 1 of 2	ENST00000308527.6	NP_695003.1
SNX33	NM_001318146.1	c.449C>T	p.Ala150Val	missense_variant	Exon 1 of 3		NP_001305075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNX33	ENST00000308527.6	c.449C>T	p.Ala150Val	missense_variant	Exon 1 of 2	1	NM_153271.2	ENSP00000311427.6
SNX33	ENST00000569152.1	c.-206C>T		upstream_gene_variant		2		ENSP00000455436.1

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

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

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

Other links and lift over

dbSNP: rs902526510; hg19: chr15-75941892;