rs139415285

Variant names:

• chr14-22773982-G-A
• rs139415285
• NM_003982.4:c.1380C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-22773982-G-A
• chr14-22773982-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4 BP6_Moderate BP7

The NM_003982.4(SLC7A7):​c.1380C>T​(p.Ile460Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC7A7 NM_003982.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.21
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• lysinuric protein intolerance

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, ClinGen, Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.204).
• BP6: Variant 14-22773982-G-A is Benign according to our data. Variant chr14-22773982-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1612372.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.21 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003982.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A7	NM_003982.4	MANE Select	c.1380C>T	p.Ile460Ile	synonymous	Exon 9 of 10	NP_003973.3
	SLC7A7	NM_001126105.3		c.1380C>T	p.Ile460Ile	synonymous	Exon 10 of 11	NP_001119577.1	A0A0S2Z502
	SLC7A7	NM_001126106.4		c.1380C>T	p.Ile460Ile	synonymous	Exon 10 of 11	NP_001119578.1	Q9UM01

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A7	ENST00000674313.1	MANE Select	c.1380C>T	p.Ile460Ile	synonymous	Exon 9 of 10	ENSP00000501493.1	Q9UM01
	SLC7A7	ENST00000397528.8	TSL:1	c.1380C>T	p.Ile460Ile	synonymous	Exon 10 of 11	ENSP00000380662.4	Q9UM01
	SLC7A7	ENST00000397529.6	TSL:1	c.1380C>T	p.Ile460Ile	synonymous	Exon 9 of 10	ENSP00000380663.2	Q9UM01

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Lysinuric protein intolerance (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		1.2

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs139415285; hg19: chr14-23243191;