Genetic Variant SNX27:p.Ser295Cys (chr1-151662247-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001330723.2(SNX27):c.883A>T(p.Ser295Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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. S295G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

SNX27
NM_001330723.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.10

Publications

4 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18535945).

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
SNX27	NM_001330723.2	MANE Select	c.883A>T	p.Ser295Cys	missense	Exon 5 of 12	NP_001317652.1
SNX27	NM_030918.6		c.883A>T	p.Ser295Cys	missense	Exon 5 of 12	NP_112180.4
SNX27	NM_001437601.1		c.580A>T	p.Ser194Cys	missense	Exon 4 of 11	NP_001424530.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SNX27	ENST00000458013.7	TSL:5 MANE Select	c.883A>T	p.Ser295Cys	missense	Exon 5 of 12	ENSP00000400333.2
SNX27	ENST00000368843.8	TSL:1	c.883A>T	p.Ser295Cys	missense	Exon 5 of 12	ENSP00000357836.3
SNX27	ENST00000368838.2	TSL:1	c.478A>T	p.Ser160Cys	missense	Exon 4 of 10	ENSP00000357831.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000399

AC:

AN:

250846

AF XY:

0.00000738

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.096

Eigen

Benign

-0.063

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.0057

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

4.1

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.6

REVEL

Benign

0.079

Sift

Benign

0.23

Sift4G

Benign

0.22

Polyphen

0.0040

Vest4

0.77

MutPred

0.56

Loss of disorder (P = 0.0018)

MVP

0.068

MPC

0.58

ClinPred

0.31

GERP RS

5.5

Varity_R

0.16

gMVP

0.62

Mutation Taster

=37/63

disease causing

(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