rs201787924

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 4P and 12B. PVS1_StrongBP6_Very_StrongBS2

The NM_022082.4(SLC17A9):c.257+2T>C variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.000738 in 1,613,210 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 1 hom., cov: 34)

Exomes 𝑓: 0.00041 ( 3 hom. )

Consequence

SLC17A9
NM_022082.4 splice_donor, intron

Scores

Splicing: ADA: 0.9897

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.12

Publications

0 publications found

Variant links:

Genes affected

SLC17A9 (HGNC:16192): (solute carrier family 17 member 9) This gene encodes a member of a family of transmembrane proteins that are involved in the transport of small molecules. The encoded protein participates in the vesicular uptake, storage, and secretion of adenoside triphosphate (ATP) and other nucleotides. A mutation in this gene was found in individuals with autosomal dominant disseminated superficial actinic porokeratosis-8. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

SLC17A9 Gene-Disease associations (from GenCC):

disseminated superficial actinic porokeratosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
porokeratosis 8, disseminated superficial actinic type
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

SLC17A9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.15102975 fraction of the gene. Cryptic splice site detected, with MaxEntScore 3.4, offset of 31, new splice context is: ctgGTgggg. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.

BP6

Variant 20-62956964-T-C is Benign according to our data. Variant chr20-62956964-T-C is described in ClinVar as [Benign]. Clinvar id is 709519.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 595 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SLC17A9	NM_022082.4 link	c.257+2T>C	splice_donor_variant, intron_variant	Intron 2 of 12	ENST00000370351.9	NP_071365.4	Q9BYT1-1
SLC17A9	NM_001302643.2 link	c.239+2T>C	splice_donor_variant, intron_variant	Intron 3 of 13		NP_001289572.2	Q9BYT1-2H0UI90
SLC17A9	XM_011528978.3 link	c.-104+28T>C	intron_variant	Intron 1 of 11		XP_011527280.1
SLC17A9	XR_936601.4 link	n.379+2T>C	splice_donor_variant, intron_variant	Intron 2 of 9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC17A9	ENST00000370351.9 link	c.257+2T>C	splice_donor_variant, intron_variant	Intron 2 of 12	1	NM_022082.4	ENSP00000359376.4	Q9BYT1-1
SLC17A9	ENST00000370349.7 link	c.239+2T>C	splice_donor_variant, intron_variant	Intron 3 of 13	1		ENSP00000359374.3	Q9BYT1-2
SLC17A9	ENST00000411611.1 link	c.317+2T>C	splice_donor_variant, intron_variant	Intron 2 of 2	2		ENSP00000388215.1	Q5W197
SLC17A9	ENST00000488738.5 link	n.377+2T>C	splice_donor_variant, intron_variant	Intron 2 of 10	2

Frequencies

GnomAD3 genomes

AF:

0.00392

AC:

596

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0131

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00288

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:

0.0000588

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.000912

AC:

225

AN:

246814

AF XY:

0.000565

show subpopulations

Gnomad AFR exome

AF:

0.0126

Gnomad AMR exome

AF:

0.000667

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.000832

GnomAD4 exome

AF:

0.000407

AC:

595

AN:

1460926

Hom.:

Cov.:

AF XY:

0.000327

AC XY:

238

AN XY:

726790

show subpopulations

African (AFR)

AF:

0.0139

AC:

465

AN:

33478

American (AMR)

AF:

0.000939

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52546

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000234

AC:

AN:

1111964

Other (OTH)

AF:

0.000944

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

115

153

191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00391

AC:

595

AN:

152284

Hom.:

Cov.:

AF XY:

0.00368

AC XY:

274

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0130

AC:

542

AN:

41556

American (AMR)

AF:

0.00287

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68006

Other (OTH)

AF:

0.00237

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

129

161

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000924

Hom.:

Bravo

AF:

0.00451

ExAC

AF:

0.00118

AC:

143

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

0.040

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

Eigen

Pathogenic

0.94

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Uncertain

0.93

PhyloP100

7.1

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Benign

0.60

SpliceAI score (max)

0.93

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.93

Position offset: -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.

rs201787924

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over