Genetic Variant SNX33:p.Phe11Phe (chr15-75649135-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_153271.2(SNX33):c.33T>C(p.Phe11Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000849 in 1,609,608 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00070 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00086 ( 2 hom. )

Consequence

SNX33
NM_153271.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.03

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 15-75649135-T-C is Benign according to our data. Variant chr15-75649135-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2645567.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.03 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX33	NM_153271.2 link	c.33T>C	p.Phe11Phe	synonymous_variant	Exon 1 of 2	ENST00000308527.6	NP_695003.1	Q8WV41
SNX33	NM_001318146.1 link	c.33T>C	p.Phe11Phe	synonymous_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.33T>C	p.Phe11Phe	synonymous_variant	Exon 1 of 2	1	NM_153271.2	ENSP00000311427.6		Q8WV41

Frequencies

GnomAD3 genomes

AF:

0.000703

AC:

107

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00100

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000769

AC:

191

AN:

248516

Hom.:

AF XY:

0.000804

AC XY:

108

AN XY:

134320

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000821

Gnomad ASJ exome

AF:

0.000204

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000332

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00125

Gnomad OTH exome

AF:

0.00116

GnomAD4 exome

AF:

0.000865

AC:

1260

AN:

1457380

Hom.:

Cov.:

AF XY:

0.000839

AC XY:

608

AN XY:

724526

show subpopulations

Gnomad4 AFR exome

AF:

0.000180

Gnomad4 AMR exome

AF:

0.000767

Gnomad4 ASJ exome

AF:

0.000232

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000326

Gnomad4 FIN exome

AF:

0.0000938

Gnomad4 NFE exome

AF:

0.00100

Gnomad4 OTH exome

AF:

0.000997

GnomAD4 genome

AF:

0.000696

AC:

106

AN:

152228

Hom.:

Cov.:

AF XY:

0.000685

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000985

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000947

Hom.:

Bravo

AF:

0.000892

EpiCase

AF:

0.00148

EpiControl

AF:

0.00154

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SNX33: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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