Variant 6-157867628-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016224.5(SNX9):c.94A>G(p.Asn32Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,166 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: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SNX9
NM_016224.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.66

Variant links:

Genes affected

SNX9 (HGNC:14973): (sorting nexin 9) This gene encodes a member of the sorting nexin family. Members of this family contain a phosphoinositide binding domain, and are involved in intracellular trafficking. The encoded protein does not contain a coiled coil region, like some family members, but does contain a SRC homology domain near its N-terminus. The encoded protein is reported to have a variety of interaction partners, including of adaptor protein 2 , dynamin, tyrosine kinase non-receptor 2, Wiskott-Aldrich syndrome-like, and ARP3 actin-related protein 3. The encoded protein is implicated in several stages of intracellular trafficking, including endocytosis, macropinocytosis, and F-actin nucleation. [provided by RefSeq, Jul 2013]

SNX9 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36760846).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNX9	NM_016224.5 linkuse as main transcript	c.94A>G	p.Asn32Asp	missense_variant	2/18	ENST00000392185.8	NP_057308.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNX9	ENST00000392185.8 linkuse as main transcript	c.94A>G	p.Asn32Asp	missense_variant	2/18	1	NM_016224.5	ENSP00000376024	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458166

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 21, 2022

The c.94A>G (p.N32D) alteration is located in exon 2 (coding exon 2) of the SNX9 gene. This alteration results from a A to G substitution at nucleotide position 94, causing the asparagine (N) at amino acid position 32 to be replaced by an aspartic acid (D). 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

0.19

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.077

T;.;T

Eigen

Benign

0.10

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.043

MetaRNN

Benign

0.37

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.67

.;.;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-2.4

.;.;N

REVEL

Benign

0.25

Sift

Benign

0.21

.;.;T

Sift4G

Pathogenic

0.0

D;D;T

Polyphen

0.99

.;.;D

Vest4

0.76

MutPred

0.42

.;.;Gain of phosphorylation at T31 (P = 0.1065);

MVP

0.46

MPC

0.37

ClinPred

0.95

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.35

gMVP

0.62

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over