chr6-157867628-A-G

Variant summary

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

The NM_016224.5(SNX9):ā€‹c.94A>Gā€‹(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 (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

SNX9
NM_016224.5 missense

Scores

1
5
13

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]

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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
SNX9NM_016224.5 linkuse as main transcriptc.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
SNX9ENST00000392185.8 linkuse as main transcriptc.94A>G p.Asn32Asp missense_variant 2/181 NM_016224.5 ENSP00000376024 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1458166
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
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.:
32

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 submitterclinical testingAmbry GeneticsNov 21, 2022The 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
T
BayesDel_noAF
Benign
-0.40
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.077
T;.;T
Eigen
Benign
0.10
Eigen_PC
Benign
0.11
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.93
D;D;D
M_CAP
Benign
0.043
D
MetaRNN
Benign
0.37
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.67
.;.;N
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.64
T
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
D
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.

Other links and lift over

hg19: chr6-158288660; API