rs386833796

Positions:

• chr14-22813290-TCTC-T

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM2 PM4_Supporting PP5_Very_Strong

The NM_003982.4(SLC7A7):​c.106_108delGAG​(p.Glu36del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SLC7A7 NM_003982.4 conservative_inframe_deletion
• Clinical Significance: Likely pathogenic criteria provided, multiple submitters, no conflicts P:3
• Conservation: PhyloP100: 8.02

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]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_003982.4. Strenght limited to Supporting due to length of the change: 1aa.
• PP5: Variant 14-22813290-TCTC-T is Pathogenic according to our data. Variant chr14-22813290-TCTC-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 56348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-22813290-TCTC-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC7A7	NM_003982.4	c.106_108delGAG	p.Glu36del	conservative_inframe_deletion	2/10	ENST00000674313.1	NP_003973.3
SLC7A7	NM_001126105.3	c.106_108delGAG	p.Glu36del	conservative_inframe_deletion	3/11		NP_001119577.1
SLC7A7	NM_001126106.4	c.106_108delGAG	p.Glu36del	conservative_inframe_deletion	3/11		NP_001119578.1
SLC7A7	XM_011537299.2	c.106_108delGAG	p.Glu36del	conservative_inframe_deletion	2/10		XP_011535601.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC7A7	ENST00000674313.1	c.106_108delGAG	p.Glu36del	conservative_inframe_deletion	2/10		NM_003982.4	ENSP00000501493.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461868 Hom.: 0 AF XY: 0.00000275 AC XY: 2 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Lysinuric protein intolerance Pathogenic:3

Likely pathogenic, criteria provided, single submitter	clinical testing	Baylor Genetics	Feb 12, 2024	- -
Likely pathogenic, no assertion criteria provided	literature only	Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	-	- -
Likely pathogenic, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Jan 14, 2022	- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs386833796; hg19: chr14-23282499;