rs61762678
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001330723.2(SNX27):c.967G>A(p.Val323Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0033 in 1,611,398 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0029 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0033 ( 15 hom. )
Consequence
SNX27
NM_001330723.2 missense
NM_001330723.2 missense
Scores
3
4
6
Clinical Significance
Conservation
PhyloP100: 9.07
Genes affected
SNX27 (HGNC:20073): (sorting nexin 27) This gene encodes a member of the sorting nexin family, a diverse group of cytoplasmic and membrane-associated proteins involved in endocytosis of plasma membrane receptors and protein trafficking through these compartments. All members of this protein family contain a phosphoinositide binding domain (PX domain). A highly similar protein in mouse is responsible for the specific recruitment of an isoform of serotonin 5-hydroxytryptamine 4 receptor into early endosomes, suggesting the analogous role for the human protein. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.010459214).
BP6
?
Variant 1-151665993-G-A is Benign according to our data. Variant chr1-151665993-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 462820.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0029 (442/152330) while in subpopulation NFE AF= 0.00435 (296/68030). AF 95% confidence interval is 0.00394. There are 2 homozygotes in gnomad4. There are 241 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High AC in GnomAd at 442 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SNX27 | NM_001330723.2 | c.967G>A | p.Val323Met | missense_variant | 6/12 | ENST00000458013.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SNX27 | ENST00000458013.7 | c.967G>A | p.Val323Met | missense_variant | 6/12 | 5 | NM_001330723.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00290 AC: 442AN: 152212Hom.: 2 Cov.: 32
GnomAD3 genomes
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442
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GnomAD3 exomes AF: 0.00316 AC: 790AN: 249942Hom.: 3 AF XY: 0.00319 AC XY: 431AN XY: 135140
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GnomAD4 exome AF: 0.00334 AC: 4879AN: 1459068Hom.: 15 Cov.: 29 AF XY: 0.00326 AC XY: 2365AN XY: 725828
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GnomAD4 genome ? AF: 0.00290 AC: 442AN: 152330Hom.: 2 Cov.: 32 AF XY: 0.00324 AC XY: 241AN XY: 74494
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ESP6500AA
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ExAC
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441
Asia WGS
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3478
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
SNX27-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 27, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Severe myoclonic epilepsy in infancy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
Polyphen
0.20, 0.24
.;B;B
Vest4
0.86, 0.85
MVP
0.85
MPC
0.68
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at