Genetic Variant SNX8:p.Ala243Ala (chr7-2264351-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_013321.4(SNX8):c.729A>G(p.Ala243Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.941 in 1,612,744 control chromosomes in the GnomAD database, including 716,873 homozygotes. 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: 𝑓 0.89 ( 61167 hom., cov: 33)

Exomes 𝑓: 0.95 ( 655706 hom. )

Consequence

SNX8
NM_013321.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -5.45

Publications

20 publications found

Variant links:

Genes affected

SNX8 (HGNC:14972): (sorting nexin 8) Enables identical protein binding activity and phosphatidylinositol binding activity. Involved in early endosome to Golgi transport and intracellular protein transport. Located in early endosome membrane. Colocalizes with retromer complex. [provided by Alliance of Genome Resources, Apr 2022]

SNX8 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP7

Synonymous conserved (PhyloP=-5.45 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX8	NM_013321.4 link	c.729A>G	p.Ala243Ala	synonymous_variant	Exon 6 of 11	ENST00000222990.8	NP_037453.1	Q9Y5X2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNX8	ENST00000222990.8 link	c.729A>G	p.Ala243Ala	synonymous_variant	Exon 6 of 11	1	NM_013321.4	ENSP00000222990.3		Q9Y5X2

Frequencies

GnomAD3 genomes

AF:

0.892

AC:

135683

AN:

152120

Hom.:

61119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.766

Gnomad AMI

AF:

0.979

Gnomad AMR

AF:

0.898

Gnomad ASJ

AF:

0.902

Gnomad EAS

AF:

0.813

Gnomad SAS

AF:

0.872

Gnomad FIN

AF:

0.956

Gnomad MID

AF:

0.924

Gnomad NFE

AF:

0.963

Gnomad OTH

AF:

0.896

GnomAD2 exomes

AF:

0.912

AC:

228377

AN:

250412

AF XY:

0.916

show subpopulations

Gnomad AFR exome

AF:

0.764

Gnomad AMR exome

AF:

0.877

Gnomad ASJ exome

AF:

0.900

Gnomad EAS exome

AF:

0.812

Gnomad FIN exome

AF:

0.957

Gnomad NFE exome

AF:

0.962

Gnomad OTH exome

AF:

0.934

GnomAD4 exome

AF:

0.946

AC:

1382115

AN:

1460506

Hom.:

655706

Cov.:

AF XY:

0.945

AC XY:

686580

AN XY:

726572

show subpopulations

African (AFR)

AF:

0.758

AC:

25363

AN:

33478

American (AMR)

AF:

0.879

AC:

39306

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.902

AC:

23578

AN:

26132

East Asian (EAS)

AF:

0.805

AC:

31963

AN:

39698

South Asian (SAS)

AF:

0.876

AC:

75526

AN:

86242

European-Finnish (FIN)

AF:

0.958

AC:

50099

AN:

52302

Middle Eastern (MID)

AF:

0.906

AC:

5222

AN:

5766

European-Non Finnish (NFE)

AF:

0.967

AC:

1074566

AN:

1111806

Other (OTH)

AF:

0.936

AC:

56492

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

3650

7300

10949

14599

18249

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21602

43204

64806

86408

108010

<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

AF:

0.892

AC:

135790

AN:

152238

Hom.:

61167

Cov.:

AF XY:

0.890

AC XY:

66280

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.766

AC:

31779

AN:

41502

American (AMR)

AF:

0.898

AC:

13737

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.902

AC:

3133

AN:

3472

East Asian (EAS)

AF:

0.813

AC:

4202

AN:

5166

South Asian (SAS)

AF:

0.872

AC:

4212

AN:

4830

European-Finnish (FIN)

AF:

0.956

AC:

10157

AN:

10624

Middle Eastern (MID)

AF:

0.932

AC:

274

AN:

294

European-Non Finnish (NFE)

AF:

0.963

AC:

65505

AN:

68034

Other (OTH)

AF:

0.898

AC:

1898

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

706

1411

2117

2822

3528

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

894

1788

2682

3576

4470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.930

Hom.:

45182

Bravo

AF:

0.883

Asia WGS

AF:

0.878

AC:

3049

AN:

3478

EpiCase

AF:

0.957

EpiControl

AF:

0.959

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.24

(source)

DANN

Benign

0.25

PhyloP100

-5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over