20-17962849-A-T

Variant names:

Variant summary

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

The NM_014426.4(SNX5):c.51+5526T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 518,922 control chromosomes in the GnomAD database, including 24,717 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 0.25 ( 5542 hom., cov: 32)

Exomes 𝑓: 0.31 ( 19175 hom. )

Consequence

SNX5
NM_014426.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.982

Publications

13 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:

SNORD17 (HGNC:32713): (small nucleolar RNA, C/D box 17)

SNORD17 links:

OVOL2 (HGNC:15804): (ovo like zinc finger 2) This gene encodes a member of the evolutionarily conserved ovo-like protein family. Mammalian members of this family contain a single zinc finger domain composed of a tetrad of C2H2 zinc fingers with variable N- and C-terminal extensions that contain intrinsically disordered domains. Members of this family are involved in epithelial development and differentiation. Knockout of this gene in mouse results in early embryonic lethality with phenotypes that include neurectoderm expansion, impaired vascularization, and heart anomalies. In humans, allelic variants of this gene have been associated with posterior polymorphous corneal dystrophy. [provided by RefSeq, Apr 2016]

OVOL2 Gene-Disease associations (from GenCC):

posterior polymorphous corneal dystrophy 1
Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
congenital hereditary endothelial dystrophy type I
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
posterior polymorphous corneal dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

OVOL2 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 (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014426.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SNX5	NM_014426.4	MANE Select	c.51+5526T>A	intron	N/A	NP_055241.1	Q9Y5X3-1
SNX5	NM_152227.3		c.51+5526T>A	intron	N/A	NP_689413.1	Q9Y5X3-1
SNX5	NM_001282454.2		c.-264-5812T>A	intron	N/A	NP_001269383.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SNX5	ENST00000377759.9	TSL:1 MANE Select	c.51+5526T>A	intron	N/A	ENSP00000366988.3	Q9Y5X3-1
SNX5	ENST00000377768.7	TSL:1	c.51+5526T>A	intron	N/A	ENSP00000366998.3	Q9Y5X3-1
SNX5	ENST00000490175.5	TSL:1	n.102-5812T>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.253

AC:

38482

AN:

151998

Hom.:

5542

Cov.:

show subpopulations

Gnomad AFR

AF:

0.117

Gnomad AMI

AF:

0.339

Gnomad AMR

AF:

0.254

Gnomad ASJ

AF:

0.326

Gnomad EAS

AF:

0.438

Gnomad SAS

AF:

0.432

Gnomad FIN

AF:

0.344

Gnomad MID

AF:

0.172

Gnomad NFE

AF:

0.291

Gnomad OTH

AF:

0.243

GnomAD2 exomes

AF:

0.307

AC:

71111

AN:

231910

AF XY:

0.315

show subpopulations

Gnomad AFR exome

AF:

0.119

Gnomad AMR exome

AF:

0.224

Gnomad ASJ exome

AF:

0.332

Gnomad EAS exome

AF:

0.449

Gnomad FIN exome

AF:

0.344

Gnomad NFE exome

AF:

0.296

Gnomad OTH exome

AF:

0.287

GnomAD4 exome

AF:

0.313

AC:

114952

AN:

366806

Hom.:

19175

Cov.:

AF XY:

0.323

AC XY:

67958

AN XY:

210340

show subpopulations

African (AFR)

AF:

0.126

AC:

1321

AN:

10506

American (AMR)

AF:

0.223

AC:

8084

AN:

36298

Ashkenazi Jewish (ASJ)

AF:

0.332

AC:

3897

AN:

11744

East Asian (EAS)

AF:

0.437

AC:

5761

AN:

13170

South Asian (SAS)

AF:

0.416

AC:

27785

AN:

66756

European-Finnish (FIN)

AF:

0.340

AC:

5746

AN:

16922

Middle Eastern (MID)

AF:

0.215

AC:

603

AN:

2810

European-Non Finnish (NFE)

AF:

0.295

AC:

56645

AN:

191970

Other (OTH)

AF:

0.307

AC:

5110

AN:

16630

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

4823

9646

14470

19293

24116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

540

1080

1620

2160

2700

<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:

0.253

AC:

38484

AN:

152116

Hom.:

5542

Cov.:

AF XY:

0.261

AC XY:

19384

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.117

AC:

4874

AN:

41520

American (AMR)

AF:

0.253

AC:

3871

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.326

AC:

1130

AN:

3466

East Asian (EAS)

AF:

0.438

AC:

2259

AN:

5158

South Asian (SAS)

AF:

0.432

AC:

2087

AN:

4828

European-Finnish (FIN)

AF:

0.344

AC:

3640

AN:

10568

Middle Eastern (MID)

AF:

0.178

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.291

AC:

19750

AN:

67976

Other (OTH)

AF:

0.243

AC:

512

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1424

2847

4271

5694

7118

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.275

Hom.:

1116

Bravo

AF:

0.236

Asia WGS

AF:

0.411

AC:

1428

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.76

PhyloP100

0.98

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

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

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over