dbSNP rs138859961: SNX27:p.Asp386Asn (chr1-151683362-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_001330723.2(SNX27):c.1156G>A(p.Asp386Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,611,482 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. D386H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

SNX27
NM_001330723.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.95

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3368088).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX27	NM_001330723.2 link	c.1156G>A	p.Asp386Asn	missense_variant	Exon 8 of 12	ENST00000458013.7	NP_001317652.1	Q96L92-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNX27	ENST00000458013.7 link	c.1156G>A	p.Asp386Asn	missense_variant	Exon 8 of 12	5	NM_001330723.2	ENSP00000400333.2		Q96L92-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1459360

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726008

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33308

American (AMR)

AF:

0.0000227

AC:

AN:

44126

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26068

East Asian (EAS)

AF:

0.00

AC:

AN:

39620

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1110998

Other (OTH)

AF:

0.0000166

AC:

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152122

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41414

American (AMR)

AF:

0.00

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2094

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.50

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

.;.;T

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Benign

0.0049

MetaRNN

Benign

0.34

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

.;L;L

PhyloP100

8.9

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-2.0

.;N;N

REVEL

Benign

0.14

Sift

Benign

0.45

.;T;T

Sift4G

Benign

0.66

.;T;T

Polyphen

0.97, 0.089

.;D;B

Vest4

0.73, 0.72

MutPred

0.42

.;Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);

MVP

0.58

MPC

0.73

ClinPred

0.75

GERP RS

5.5

Varity_R

0.24

gMVP

0.61

Mutation Taster

=69/31

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs138859961

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over