rs79987078

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP5

The NM_014270.5(SLC7A9):c.368C>T(p.Thr123Met) variant causes a missense change. The variant allele was found at a frequency of 0.000236 in 1,614,210 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T123T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

SLC7A9
NM_014270.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:10U:5

Conservation

PhyloP100: 5.44

Publications

16 publications found

Variant links:

Genes affected

SLC7A9 (HGNC:11067): (solute carrier family 7 member 9) This gene encodes a protein that belongs to a family of light subunits of amino acid transporters. This protein plays a role in the high-affinity and sodium-independent transport of cystine and neutral and dibasic amino acids, and appears to function in the reabsorption of cystine in the kidney tubule. Mutations in this gene cause non-type I cystinuria, a disease that leads to cystine stones in the urinary system due to impaired transport of cystine and dibasic amino acids. Alternate transcript variants, which encode the same protein, have been found for this gene. [provided by RefSeq, Jul 2011]

SLC7A9 Gene-Disease associations (from GenCC):

cystinuria
Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, ClinGen
cystinuria type B
Inheritance: SD Classification: SUPPORTIVE Submitted by: Orphanet

SLC7A9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP5

Variant 19-32864206-G-A is Pathogenic according to our data. Variant chr19-32864206-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 5793.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014270.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC7A9	NM_014270.5	MANE Select	c.368C>T	p.Thr123Met	missense	Exon 4 of 13	NP_055085.1	P82251
SLC7A9	NM_001126335.2		c.368C>T	p.Thr123Met	missense	Exon 4 of 13	NP_001119807.1	P82251
SLC7A9	NM_001243036.2		c.368C>T	p.Thr123Met	missense	Exon 4 of 13	NP_001229965.1	P82251

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC7A9	ENST00000023064.9	TSL:1 MANE Select	c.368C>T	p.Thr123Met	missense	Exon 4 of 13	ENSP00000023064.3	P82251
SLC7A9	ENST00000587772.1	TSL:1	c.368C>T	p.Thr123Met	missense	Exon 4 of 13	ENSP00000468439.1	P82251
SLC7A9	ENST00000590341.5	TSL:1	c.368C>T	p.Thr123Met	missense	Exon 4 of 13	ENSP00000464822.1	P82251

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

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:

0.000279

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000195

AC:

AN:

251344

AF XY:

0.000147

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000282

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000238

AC:

348

AN:

1461860

Hom.:

Cov.:

AF XY:

0.000226

AC XY:

164

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.000179

AC:

AN:

33480

American (AMR)

AF:

0.000380

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000281

AC:

312

AN:

1111992

Other (OTH)

AF:

0.000199

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

110

138

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000217

AC:

AN:

152350

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41600

American (AMR)

AF:

0.000457

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000294

AC:

AN:

68020

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000250

Hom.:

Bravo

AF:

0.000287

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000140

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000356

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cystinuria (11)

not provided (4)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Uncertain

0.054

BayesDel_noAF

Pathogenic

0.15

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.75

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.54

MetaSVM

Uncertain

0.14

MutationAssessor

Benign

1.4

PhyloP100

5.4

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.53

Sift

Benign

0.031

Sift4G

Uncertain

0.031

Polyphen

0.018

Vest4

0.39

MVP

0.86

MPC

0.84

ClinPred

0.13

GERP RS

4.0

Varity_R

0.46

gMVP

0.76

Mutation Taster

=2/98

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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