dbSNP rs35296149: SNX7:p.Ser123Thr (chr1-98691078-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015976.5(SNX7):c.367T>A(p.Ser123Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 1,600,472 control chromosomes in the GnomAD database, including 3,594 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.032 ( 377 hom., cov: 32)

Exomes 𝑓: 0.027 ( 3217 hom. )

Consequence

SNX7
NM_015976.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.70

Publications

7 publications found

Variant links:

Genes affected

SNX7 (HGNC:14971): (sorting nexin 7) 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 does not contain a coiled coil region like some family members, and its exact function is unknown. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 11. [provided by RefSeq, Jun 2010]

SNX7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012304187).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNX7	NM_015976.5 link	c.367T>A	p.Ser123Thr	missense_variant	Exon 3 of 9	ENST00000306121.8	NP_057060.2	Q9UNH6-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNX7	ENST00000306121.8 link	c.367T>A	p.Ser123Thr	missense_variant	Exon 3 of 9	1	NM_015976.5	ENSP00000304429.3		Q9UNH6-3

Frequencies

GnomAD3 genomes

AF:

0.0319

AC:

4845

AN:

152036

Hom.:

373

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0149

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.0691

Gnomad ASJ

AF:

0.00894

Gnomad EAS

AF:

0.342

Gnomad SAS

AF:

0.0552

Gnomad FIN

AF:

0.0239

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0113

Gnomad OTH

AF:

0.0273

GnomAD2 exomes

AF:

0.0586

AC:

14413

AN:

245792

AF XY:

0.0527

show subpopulations

Gnomad AFR exome

AF:

0.0150

Gnomad AMR exome

AF:

0.144

Gnomad ASJ exome

AF:

0.00914

Gnomad EAS exome

AF:

0.347

Gnomad FIN exome

AF:

0.0222

Gnomad NFE exome

AF:

0.0115

Gnomad OTH exome

AF:

0.0352

GnomAD4 exome

AF:

0.0267

AC:

38674

AN:

1448318

Hom.:

3217

Cov.:

AF XY:

0.0264

AC XY:

19042

AN XY:

721026

show subpopulations

African (AFR)

AF:

0.0158

AC:

518

AN:

32888

American (AMR)

AF:

0.135

AC:

5878

AN:

43628

Ashkenazi Jewish (ASJ)

AF:

0.0102

AC:

263

AN:

25808

East Asian (EAS)

AF:

0.349

AC:

13629

AN:

39036

South Asian (SAS)

AF:

0.0393

AC:

3339

AN:

84938

European-Finnish (FIN)

AF:

0.0215

AC:

1143

AN:

53162

Middle Eastern (MID)

AF:

0.00711

AC:

AN:

5622

European-Non Finnish (NFE)

AF:

0.0108

AC:

11959

AN:

1103448

Other (OTH)

AF:

0.0319

AC:

1905

AN:

59788

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

1491

2982

4472

5963

7454

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

716

1432

2148

2864

3580

<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:

0.0320

AC:

4864

AN:

152154

Hom.:

377

Cov.:

AF XY:

0.0355

AC XY:

2642

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0150

AC:

622

AN:

41552

American (AMR)

AF:

0.0700

AC:

1070

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00894

AC:

AN:

3468

East Asian (EAS)

AF:

0.342

AC:

1763

AN:

5156

South Asian (SAS)

AF:

0.0560

AC:

270

AN:

4818

European-Finnish (FIN)

AF:

0.0239

AC:

254

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0113

AC:

765

AN:

67934

Other (OTH)

AF:

0.0284

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

211

422

633

844

1055

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0223

Hom.:

215

Bravo

AF:

0.0387

TwinsUK

AF:

0.0127

AC:

ALSPAC

AF:

0.0127

AC:

ESP6500AA

AF:

0.0138

AC:

ESP6500EA

AF:

0.0127

AC:

109

ExAC

AF:

0.0552

AC:

6705

Asia WGS

AF:

0.158

AC:

549

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.29

DEOGEN2

Benign

0.0058

T;.;T

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.42

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.65

T;T;T

MetaRNN

Benign

0.0012

T;T;T

MetaSVM

Benign

-0.96

PhyloP100

2.7

PrimateAI

Uncertain

0.59

PROVEAN

Benign

1.5

N;N;N

REVEL

Benign

0.053

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.027

B;B;.

Vest4

0.16

MPC

0.080

ClinPred

0.013

GERP RS

3.6

gMVP

0.30

Mutation Taster

=94/6

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