chr19-32830640-G-A

Position:

chr19-32830640-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM5BP4_StrongBP6_Very_StrongBS1BS2

The NM_014270.5(SLC7A9):c.1444C>T(p.Pro482Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000639 in 1,613,982 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P482L) has been classified as Likely pathogenic.

Frequency

Genomes: 𝑓 0.0035 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00035 ( 5 hom. )

Consequence

SLC7A9
NM_014270.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.40

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

PM5

Other missense variant is known to change same aminoacid residue: Variant chrnull-null-null-null is described in UniProt as null.

BP4

Computational evidence support a benign effect (MetaRNN=0.0071748793).

BP6

Variant 19-32830640-G-A is Benign according to our data. Variant chr19-32830640-G-A is described in ClinVar as [Benign]. Clinvar id is 783828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-32830640-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00345 (526/152310) while in subpopulation AFR AF= 0.0123 (513/41556). AF 95% confidence interval is 0.0115. There are 1 homozygotes in gnomad4. There are 265 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 5 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A9	NM_014270.5 linkuse as main transcript	c.1444C>T	p.Pro482Ser	missense_variant	13/13	ENST00000023064.9	NP_055085.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A9	ENST00000023064.9 linkuse as main transcript	c.1444C>T	p.Pro482Ser	missense_variant	13/13	1	NM_014270.5	ENSP00000023064	P1

Frequencies

GnomAD3 genomes

AF:

0.00344

AC:

524

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0123

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:

0.00316

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000843

AC:

212

AN:

251488

Hom.:

AF XY:

0.000677

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.0114

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000346

AC:

506

AN:

1461672

Hom.:

Cov.:

AF XY:

0.000294

AC XY:

214

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.0128

Gnomad4 AMR exome

AF:

0.000581

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000450

Gnomad4 OTH exome

AF:

0.000646

GnomAD4 genome

AF:

0.00345

AC:

526

AN:

152310

Hom.:

Cov.:

AF XY:

0.00356

AC XY:

265

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0123

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000473

Hom.:

Bravo

AF:

0.00373

ESP6500AA

AF:

0.0111

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00107

AC:

130

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 15, 2024	- -

SLC7A9-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Uncertain

0.0

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

T;T;T

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.35

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.84

.;.;T

MetaRNN

Benign

0.0072

T;T;T

MetaSVM

Uncertain

-0.26

MutationAssessor

Benign

1.8

L;L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.2

.;N;.

REVEL

Uncertain

0.47

Sift

Benign

0.16

.;T;.

Sift4G

Uncertain

0.041

D;D;D

Polyphen

0.017

B;B;B

Vest4

0.15

MVP

0.75

MPC

0.31

ClinPred

0.025

GERP RS

3.5

Varity_R

0.13

gMVP

0.46

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

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