Variant 19-32830541-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014270.5(SLC7A9):c.*79T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,086,512 control chromosomes in the GnomAD database, including 15,484 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2442 hom., cov: 32)

Exomes 𝑓: 0.16 ( 13042 hom. )

Consequence

SLC7A9
NM_014270.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.408

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 (BayesDel_noAF=-0.86).

BP6

Variant 19-32830541-A-G is Benign according to our data. Variant chr19-32830541-A-G is described in ClinVar as [Benign]. Clinvar id is 328740.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-32830541-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A9	NM_014270.5 linkuse as main transcript	c.*79T>C		3_prime_UTR_variant	13/13	ENST00000023064.9	NP_055085.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
SLC7A9	ENST00000023064.9 linkuse as main transcript	c.*79T>C	3_prime_UTR_variant	13/13	1	NM_014270.5	ENSP00000023064	P1
SLC7A9	ENST00000590341.5 linkuse as main transcript	c.*79T>C	3_prime_UTR_variant	13/13	1		ENSP00000464822	P1
SLC7A9	ENST00000590465.5 linkuse as main transcript	c.*1690T>C	3_prime_UTR_variant, NMD_transcript_variant	9/9	2		ENSP00000468076
SLC7A9	ENST00000592232.5 linkuse as main transcript		downstream_gene_variant		1		ENSP00000465563

Frequencies

GnomAD3 genomes

AF:

0.174

AC:

26531

AN:

152058

Hom.:

2438

Cov.:

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.178

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.142

Gnomad EAS

AF:

0.200

Gnomad SAS

AF:

0.124

Gnomad FIN

AF:

0.235

Gnomad MID

AF:

0.156

Gnomad NFE

AF:

0.166

Gnomad OTH

AF:

0.165

GnomAD4 exome

AF:

0.163

AC:

152149

AN:

934336

Hom.:

13042

Cov.:

AF XY:

0.162

AC XY:

78821

AN XY:

488020

show subpopulations

Gnomad4 AFR exome

AF:

0.196

Gnomad4 AMR exome

AF:

0.100

Gnomad4 ASJ exome

AF:

0.139

Gnomad4 EAS exome

AF:

0.209

Gnomad4 SAS exome

AF:

0.130

Gnomad4 FIN exome

AF:

0.216

Gnomad4 NFE exome

AF:

0.163

Gnomad4 OTH exome

AF:

0.171

GnomAD4 genome

AF:

0.175

AC:

26559

AN:

152176

Hom.:

2442

Cov.:

AF XY:

0.174

AC XY:

12979

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.197

Gnomad4 AMR

AF:

0.127

Gnomad4 ASJ

AF:

0.142

Gnomad4 EAS

AF:

0.200

Gnomad4 SAS

AF:

0.123

Gnomad4 FIN

AF:

0.235

Gnomad4 NFE

AF:

0.166

Gnomad4 OTH

AF:

0.169

Alfa

AF:

0.152

Hom.:

1718

Bravo

AF:

0.169

Asia WGS

AF:

0.188

AC:

653

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 11, 2020	- -

Cystinuria

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

DANN

Benign

0.64

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