14-22773619-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003982.4(SLC7A7):c.1527A>G(p.Lys509=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 1,613,208 control chromosomes in the GnomAD database, including 627,464 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.79 ( 49738 hom., cov: 31)

Exomes 𝑓: 0.89 ( 577726 hom. )

Consequence

SLC7A7
NM_003982.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9O:1

Conservation

PhyloP100: -0.309

Variant links:

Genes affected

SLC7A7 (HGNC:11065): (solute carrier family 7 member 7) The protein encoded by this gene is the light subunit of a cationic amino acid transporter. This sodium-independent transporter is formed when the light subunit encoded by this gene dimerizes with the heavy subunit transporter protein SLC3A2. This transporter is found in epithelial cell membranes where it transfers cationic and large neutral amino acids from the cell to the extracellular space. Defects in this gene are a cause of lysinuric protein intolerance (LPI). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2011]

SLC7A7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 14-22773619-T-C is Benign according to our data. Variant chr14-22773619-T-C is described in ClinVar as [Benign]. Clinvar id is 139197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-22773619-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.309 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC7A7	NM_003982.4 linkuse as main transcript	c.1527A>G	p.Lys509=	synonymous_variant	10/10	ENST00000674313.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC7A7	ENST00000674313.1 linkuse as main transcript	c.1527A>G	p.Lys509=	synonymous_variant	10/10		NM_003982.4	P1

Frequencies

GnomAD3 genomes

AF:

0.790

AC:

120034

AN:

152008

Hom.:

49708

Cov.:

show subpopulations

Gnomad AFR

AF:

0.512

Gnomad AMI

AF:

0.957

Gnomad AMR

AF:

0.891

Gnomad ASJ

AF:

0.912

Gnomad EAS

AF:

0.928

Gnomad SAS

AF:

0.885

Gnomad FIN

AF:

0.861

Gnomad MID

AF:

0.896

Gnomad NFE

AF:

0.897

Gnomad OTH

AF:

0.815

GnomAD3 exomes

AF:

0.876

AC:

220346

AN:

251398

Hom.:

97899

AF XY:

0.883

AC XY:

119936

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.509

Gnomad AMR exome

AF:

0.939

Gnomad ASJ exome

AF:

0.918

Gnomad EAS exome

AF:

0.934

Gnomad SAS exome

AF:

0.896

Gnomad FIN exome

AF:

0.863

Gnomad NFE exome

AF:

0.894

Gnomad OTH exome

AF:

0.878

GnomAD4 exome

AF:

0.887

AC:

1295830

AN:

1461080

Hom.:

577726

Cov.:

AF XY:

0.889

AC XY:

646073

AN XY:

726892

show subpopulations

Gnomad4 AFR exome

AF:

0.492

Gnomad4 AMR exome

AF:

0.932

Gnomad4 ASJ exome

AF:

0.915

Gnomad4 EAS exome

AF:

0.918

Gnomad4 SAS exome

AF:

0.898

Gnomad4 FIN exome

AF:

0.862

Gnomad4 NFE exome

AF:

0.896

Gnomad4 OTH exome

AF:

0.879

GnomAD4 genome

AF:

0.790

AC:

120112

AN:

152128

Hom.:

49738

Cov.:

AF XY:

0.793

AC XY:

58948

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.513

Gnomad4 AMR

AF:

0.892

Gnomad4 ASJ

AF:

0.912

Gnomad4 EAS

AF:

0.928

Gnomad4 SAS

AF:

0.886

Gnomad4 FIN

AF:

0.861

Gnomad4 NFE

AF:

0.897

Gnomad4 OTH

AF:

0.817

Alfa

AF:

0.883

Hom.:

142858

Bravo

AF:

0.781

Asia WGS

AF:

0.894

AC:

3108

AN:

3478

EpiCase

AF:

0.905

EpiControl

AF:

0.904

ClinVar

Significance: Benign

Submissions summary: Benign:9Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 25, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 100% of patients studied by a panel of primary immunodeficiencies. Number of patients: 95. Only high quality variants are reported. -

Lysinuric protein intolerance

Benign:4

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not provided

Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

Cadd

Benign

2.5

Dann

Benign

0.69

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