11-65852642-C-T

Variant summary

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

The NM_152760.3(SNX32):c.925C>T(p.Arg309Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000317 in 1,606,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

SNX32
NM_152760.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0250

Variant links:

Genes affected

SNX32 (HGNC:26423): (sorting nexin 32) Predicted to enable phosphatidylinositol binding activity. Predicted to be involved in retrograde transport, endosome to Golgi. Predicted to be located in cytosol. Predicted to be active in endosome. [provided by Alliance of Genome Resources, Apr 2022]

SNX32 links:

CFL1 (HGNC:1874): (cofilin 1) The protein encoded by this gene can polymerize and depolymerize F-actin and G-actin in a pH-dependent manner. Increased phosphorylation of this protein by LIM kinase aids in Rho-induced reorganization of the actin cytoskeleton. Cofilin is a widely distributed intracellular actin-modulating protein that binds and depolymerizes filamentous F-actin and inhibits the polymerization of monomeric G-actin in a pH-dependent manner. It is involved in the translocation of actin-cofilin complex from cytoplasm to nucleus.[supplied by OMIM, Apr 2004]

CFL1 links:

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=0.2595523).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNX32	NM_152760.3 linkuse as main transcript	c.925C>T	p.Arg309Trp	missense_variant	11/13	ENST00000308342.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNX32	ENST00000308342.7 linkuse as main transcript	c.925C>T	p.Arg309Trp	missense_variant	11/13	1	NM_152760.3	P1	Q86XE0-1
SNX32	ENST00000530101.5 linkuse as main transcript	n.1415C>T		non_coding_transcript_exon_variant	9/11	2
CFL1	ENST00000527752.1 linkuse as main transcript	n.61+5455G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000302

AC:

AN:

231946

Hom.:

AF XY:

0.0000237

AC XY:

AN XY:

126662

show subpopulations

Gnomad AFR exome

AF:

0.000274

Gnomad AMR exome

AF:

0.0000303

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:

0.0000194

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000234

AC:

AN:

1454532

Hom.:

Cov.:

AF XY:

0.0000180

AC XY:

AN XY:

723542

show subpopulations

Gnomad4 AFR exome

AF:

0.000540

Gnomad4 AMR exome

AF:

0.0000458

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000760

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000721

Gnomad4 OTH exome

AF:

0.0000499

GnomAD4 genome

AF:

0.000112

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.000362

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000106

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000331

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2023

The c.925C>T (p.R309W) alteration is located in exon 11 (coding exon 11) of the SNX32 gene. This alteration results from a C to T substitution at nucleotide position 925, causing the arginine (R) at amino acid position 309 to be replaced by a tryptophan (W). 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

Pathogenic

0.94

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.29

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.36

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.40

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.0070

MetaRNN

Benign

0.26

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.0

MutationTaster

Benign

0.93

PrimateAI

Benign

0.30

PROVEAN

Pathogenic

-6.8

REVEL

Benign

0.21

Sift

Pathogenic

0.0

Sift4G

Benign

0.074

Polyphen

0.027

Vest4

0.45

MVP

0.40

MPC

0.094

ClinPred

0.40

GERP RS

1.1

Varity_R

0.51

gMVP

0.45

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