dbSNP rs2273448: SNX5:p.Glu181Asp (chr20-17951566-C-G) – 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_014426.4(SNX5):c.543G>C(p.Glu181Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,488 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.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SNX5
NM_014426.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.466

Publications

0 publications found

Variant links:

Genes affected

SNX5 (HGNC:14969): (sorting nexin 5) This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. This protein functions in endosomal sorting, the phosphoinositide-signaling pathway, and macropinocytosis. This gene may play a role in the tumorigenesis of papillary thyroid carcinoma. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2013]

SNX5 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=0.2735566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
SNX5	NM_014426.4 link	c.543G>C	p.Glu181Asp	missense_variant	Exon 6 of 13	ENST00000377759.9	NP_055241.1
SNX5	NM_152227.3 link	c.543G>C	p.Glu181Asp	missense_variant	Exon 7 of 14		NP_689413.1
SNX5	NM_001282454.2 link	c.228G>C	p.Glu76Asp	missense_variant	Exon 6 of 13		NP_001269383.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNX5	ENST00000377759.9 link	c.543G>C	p.Glu181Asp	missense_variant	Exon 6 of 13	1	NM_014426.4	ENSP00000366988.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459488

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726170

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33428

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39652

South Asian (SAS)

AF:

0.00

AC:

AN:

86172

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5046

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110692

Other (OTH)

AF:

0.00

AC:

AN:

60244

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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 v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.75

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;T;T;T

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.93

.;D;D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.27

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.3

M;M;.;.

PhyloP100

0.47

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-2.0

N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.086

T;T;T;T

Sift4G

Benign

0.14

T;T;T;.

Polyphen

0.99

D;D;.;.

Vest4

0.55

MutPred

0.37

Gain of MoRF binding (P = 0.0725);Gain of MoRF binding (P = 0.0725);.;.;

MVP

0.52

MPC

0.40

ClinPred

0.78

GERP RS

4.3

PromoterAI

0.029

Neutral

(source)

Varity_R

0.17

gMVP

0.33

Mutation Taster

=87/13

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over