dbSNP rs1354158738: SNX27:p.Gly40Ser (chr1-151612319-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001330723.2(SNX27):c.118G>A(p.Gly40Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000073 in 1,369,532 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 (★). Synonymous variant affecting the same amino acid position (i.e. G40G) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

SNX27
NM_001330723.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.02

Publications

0 publications found

Variant links:

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]

SNX27 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia

SNX27 links:

ENSG00000250734 (HGNC:):

ENSG00000250734 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4213669).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330723.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNX27	NM_001330723.2	MANE Select	c.118G>A	p.Gly40Ser	missense	Exon 1 of 12	NP_001317652.1	Q96L92-1
SNX27	NM_030918.6		c.118G>A	p.Gly40Ser	missense	Exon 1 of 12	NP_112180.4
SNX27	NM_001437601.1		c.118G>A	p.Gly40Ser	missense	Exon 1 of 11	NP_001424530.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SNX27	ENST00000458013.7	TSL:5 MANE Select	c.118G>A	p.Gly40Ser	missense	Exon 1 of 12	ENSP00000400333.2	Q96L92-1
SNX27	ENST00000368843.8	TSL:1	c.118G>A	p.Gly40Ser	missense	Exon 1 of 12	ENSP00000357836.3	Q96L92-3
SNX27	ENST00000368841.7	TSL:1	n.118G>A		non_coding_transcript_exon	Exon 1 of 12	ENSP00000357834.2	H7C603

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.30e-7

AC:

AN:

1369532

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

676758

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28424

American (AMR)

AF:

0.00

AC:

AN:

29706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23524

East Asian (EAS)

AF:

0.00

AC:

AN:

31214

South Asian (SAS)

AF:

0.00

AC:

AN:

76188

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46974

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5542

European-Non Finnish (NFE)

AF:

9.34e-7

AC:

AN:

1071164

Other (OTH)

AF:

0.00

AC:

AN:

56796

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Severe myoclonic epilepsy in infancy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Uncertain

0.031

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.84

M_CAP

Pathogenic

0.86

MetaRNN

Benign

0.42

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

PhyloP100

6.0

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-1.2

REVEL

Benign

0.21

Sift

Uncertain

0.010

Sift4G

Uncertain

0.052

Polyphen

1.0

Vest4

0.42

MutPred

0.45

Gain of phosphorylation at G40 (P = 0.0174)

MVP

0.13

MPC

1.4

ClinPred

0.83

GERP RS

3.0

PromoterAI

-0.035

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.9

Varity_R

0.50

gMVP

0.48

Mutation Taster

=58/42

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over