Genetic Variant SNX27:p.Gly6Ala (chr1-151612218-G-C) – 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.17G>C(p.Gly6Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000821 in 1,218,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G6R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.2e-7 ( 0 hom. )

Consequence

SNX27
NM_001330723.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.36

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 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=0.3871838).

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.17G>C	p.Gly6Ala	missense	Exon 1 of 12	NP_001317652.1	Q96L92-1
SNX27	NM_030918.6		c.17G>C	p.Gly6Ala	missense	Exon 1 of 12	NP_112180.4
SNX27	NM_001437601.1		c.17G>C	p.Gly6Ala	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.17G>C	p.Gly6Ala	missense	Exon 1 of 12	ENSP00000400333.2	Q96L92-1
SNX27	ENST00000368843.8	TSL:1	c.17G>C	p.Gly6Ala	missense	Exon 1 of 12	ENSP00000357836.3	Q96L92-3
SNX27	ENST00000368841.7	TSL:1	n.17G>C		non_coding_transcript_exon	Exon 1 of 12	ENSP00000357834.2	H7C603

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.21e-7

AC:

AN:

1218672

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

590812

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24458

American (AMR)

AF:

0.00

AC:

AN:

11910

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17170

East Asian (EAS)

AF:

0.00

AC:

AN:

27198

South Asian (SAS)

AF:

0.00

AC:

AN:

55280

European-Finnish (FIN)

AF:

0.0000277

AC:

AN:

36076

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4580

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

992214

Other (OTH)

AF:

0.00

AC:

AN:

49786

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

-0.15

Eigen_PC

Benign

0.0023

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.83

M_CAP

Pathogenic

0.80

MetaRNN

Benign

0.39

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

6.4

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.63

REVEL

Benign

0.24

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.024

Polyphen

0.16

Vest4

0.41

MutPred

0.38

Loss of loop (P = 0.0288)

MVP

0.74

MPC

1.6

ClinPred

0.75

GERP RS

3.1

PromoterAI

0.28

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.41

gMVP

0.64

Mutation Taster

=74/26

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over