rs386833792

Variant names:

• chr14-22813385-G-A
• rs386833792
• NM_003982.4:c.14C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-22813385-G-A
• chr14-22813385-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_003982.4(SLC7A7):​c.14C>T​(p.Thr5Ile) variant causes a missense 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 Conflicting classifications of pathogenicity (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC7A7 NM_003982.4 missense
• Clinical Significance: Conflicting classifications of pathogenicity no assertion criteria provided P:1 U:1
• Conservation: PhyloP100: -0.344
• Publications: 1 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: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 14-22813385-G-A is Pathogenic according to our data. Variant chr14-22813385-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 56344.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.2850808). . Strength limited to SUPPORTING due to the PP5.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A7	NM_003982.4	MANE Select	c.14C>T	p.Thr5Ile	missense	Exon 2 of 10	NP_003973.3
	SLC7A7	NM_001126105.3		c.14C>T	p.Thr5Ile	missense	Exon 3 of 11	NP_001119577.1
	SLC7A7	NM_001126106.4		c.14C>T	p.Thr5Ile	missense	Exon 3 of 11	NP_001119578.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A7	ENST00000674313.1	MANE Select	c.14C>T	p.Thr5Ile	missense	Exon 2 of 10	ENSP00000501493.1
	SLC7A7	ENST00000397528.8	TSL:1	c.14C>T	p.Thr5Ile	missense	Exon 3 of 11	ENSP00000380662.4
	SLC7A7	ENST00000397529.6	TSL:1	c.14C>T	p.Thr5Ile	missense	Exon 2 of 10	ENSP00000380663.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Conflicting classifications of pathogenicity

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	1	-	Lysinuric protein intolerance (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	2.7
DANN	Benign	0.43
DEOGEN2	Benign	0.12	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.34
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.99	N
REVEL	Uncertain	0.52
Sift	Benign	0.079	T
Sift4G	Benign	0.25	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.71		Loss of phosphorylation at V5 (P = 0.0223)
MVP		0.16
MPC		0.21
ClinPred		0.18	T
GERP RS		-7.7
Varity_R		0.059
gMVP		0.58
Mutation Taster		=5/95	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs386833792; hg19: chr14-23282594;