rs80283711

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014270.5(SLC7A9):c.1403C>T(p.Pro468Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00104 in 1,613,602 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 14 hom. )

Consequence

SLC7A9
NM_014270.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:3

Conservation

PhyloP100: 7.00

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008548379).

BP6

Variant 19-32830681-G-A is Benign according to our data. Variant chr19-32830681-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 328743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00109 (166/152292) while in subpopulation EAS AF= 0.00772 (40/5180). AF 95% confidence interval is 0.00583. There are 1 homozygotes in gnomad4. There are 89 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 14 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC7A9	NM_014270.5 link	c.1403C>T	p.Pro468Leu	missense_variant	Exon 13 of 13	ENST00000023064.9	NP_055085.1	P82251

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC7A9	ENST00000023064.9 link	c.1403C>T	p.Pro468Leu	missense_variant	Exon 13 of 13	1	NM_014270.5	ENSP00000023064.3		P82251

Frequencies

GnomAD3 genomes

AF:

0.00108

AC:

164

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00642

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00770

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00317

AC:

797

AN:

251482

Hom.:

AF XY:

0.00260

AC XY:

353

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0173

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00696

Gnomad SAS exome

AF:

0.00170

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00104

AC:

1518

AN:

1461310

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

745

AN XY:

726992

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0167

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0130

Gnomad4 SAS exome

AF:

0.00179

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000450

Gnomad4 OTH exome

AF:

0.000812

GnomAD4 genome

AF:

0.00109

AC:

166

AN:

152292

Hom.:

Cov.:

AF XY:

0.00120

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00667

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00772

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000882

Hom.:

Bravo

AF:

0.00176

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00273

AC:

332

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cystinuria

Pathogenic:1Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Aug 26, 2024

Chinese Inherited Urolithiasis Consortium, The Affiliated Yantai Yuhuangding Hospital of Qingdao University

Significance: Likely pathogenic

Review Status: no assertion criteria provided

Collection Method: clinical testing

Variant_type:missense/MutationTaster:Disease_causing/CADD:Damaging/phyloP:Conserved/phastCons:Conserved/gnomAD_exome_EastAsian:0.0074/ExAC_EastAsian:0.0081/dbSNP:rs80283711 -

not provided

Benign:2

Jan 26, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.085

BayesDel_noAF

Uncertain

0.12

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.40

T;T;T

Eigen

Benign

-0.019

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

.;.;D

MetaRNN

Benign

0.0085

T;T;T

MetaSVM

Uncertain

-0.12

MutationAssessor

Uncertain

2.8

M;M;M

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.2

.;N;.

REVEL

Uncertain

0.54

Sift

Benign

0.62

.;T;.

Sift4G

Benign

0.48

T;T;T

Polyphen

0.15

B;B;B

Vest4

0.67

MVP

0.91

MPC

0.55

ClinPred

1.0

GERP RS

5.7

Varity_R

0.13

gMVP

0.65

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over