14-22778903-A-G

Position:

chr14-22778903-A-G

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_003982.4(SLC7A7):c.660T>C(p.Gly220Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 1,613,810 control chromosomes in the GnomAD database, including 20,802 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 2989 hom., cov: 32)

Exomes 𝑓: 0.15 ( 17813 hom. )

Consequence

SLC7A7
NM_003982.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.623

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:

SLC7A7 (HGNC:):

SLC7A7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 14-22778903-A-G is Benign according to our data. Variant chr14-22778903-A-G is described in ClinVar as [Benign]. Clinvar id is 139196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-22778903-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.623 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A7	NM_003982.4 linkuse as main transcript	c.660T>C	p.Gly220Gly	synonymous_variant	4/10	ENST00000674313.1	NP_003973.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A7	ENST00000674313.1 linkuse as main transcript	c.660T>C	p.Gly220Gly	synonymous_variant	4/10		NM_003982.4	ENSP00000501493.1		Q9UM01

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28155

AN:

151982

Hom.:

2975

Cov.:

show subpopulations

Gnomad AFR

AF:

0.254

Gnomad AMI

AF:

0.129

Gnomad AMR

AF:

0.256

Gnomad ASJ

AF:

0.0997

Gnomad EAS

AF:

0.341

Gnomad SAS

AF:

0.121

Gnomad FIN

AF:

0.149

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.131

Gnomad OTH

AF:

0.179

GnomAD3 exomes

AF:

0.186

AC:

46620

AN:

251284

Hom.:

5648

AF XY:

0.173

AC XY:

23526

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.256

Gnomad AMR exome

AF:

0.360

Gnomad ASJ exome

AF:

0.0928

Gnomad EAS exome

AF:

0.351

Gnomad SAS exome

AF:

0.116

Gnomad FIN exome

AF:

0.143

Gnomad NFE exome

AF:

0.132

Gnomad OTH exome

AF:

0.165

GnomAD4 exome

AF:

0.146

AC:

213548

AN:

1461710

Hom.:

17813

Cov.:

AF XY:

0.144

AC XY:

104497

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.251

Gnomad4 AMR exome

AF:

0.342

Gnomad4 ASJ exome

AF:

0.0941

Gnomad4 EAS exome

AF:

0.318

Gnomad4 SAS exome

AF:

0.117

Gnomad4 FIN exome

AF:

0.146

Gnomad4 NFE exome

AF:

0.132

Gnomad4 OTH exome

AF:

0.148

GnomAD4 genome

AF:

0.185

AC:

28197

AN:

152100

Hom.:

2989

Cov.:

AF XY:

0.186

AC XY:

13852

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.254

Gnomad4 AMR

AF:

0.257

Gnomad4 ASJ

AF:

0.0997

Gnomad4 EAS

AF:

0.341

Gnomad4 SAS

AF:

0.120

Gnomad4 FIN

AF:

0.149

Gnomad4 NFE

AF:

0.131

Gnomad4 OTH

AF:

0.182

Alfa

AF:

0.140

Hom.:

2800

Bravo

AF:

0.198

Asia WGS

AF:

0.236

AC:

818

AN:

3478

EpiCase

AF:

0.124

EpiControl

AF:

0.128

ClinVar

Significance: Benign

Submissions summary: Benign:9Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 04, 2014	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, 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 42% of patients studied by a panel of primary immunodeficiencies. Number of patients: 40. Only high quality variants are reported. -
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+	-	- -

Lysinuric protein intolerance

Benign:4

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:1Other: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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

3.5

DANN

Benign

0.72

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