14-22780330-A-C

Variant names:

• chr14-22780330-A-C
• rs12433985
• NM_003982.4:c.500-279T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003982.4(SLC7A7):​c.500-279T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000801 in 249,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000080 (0 hom.)
• Consequence: SLC7A7 NM_003982.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.58
• Publications: 10 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 (BayesDel_noAF=-0.84).

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.500-279T>G		intron	N/A	NP_003973.3
	SLC7A7	NM_001126105.3		c.500-279T>G		intron	N/A	NP_001119577.1	A0A0S2Z502
	SLC7A7	NM_001126106.4		c.500-279T>G		intron	N/A	NP_001119578.1	Q9UM01

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A7	ENST00000674313.1	MANE Select	c.500-279T>G		intron	N/A	ENSP00000501493.1	Q9UM01
	SLC7A7	ENST00000397528.8	TSL:1	c.500-279T>G		intron	N/A	ENSP00000380662.4	Q9UM01
	SLC7A7	ENST00000397529.6	TSL:1	c.500-279T>G		intron	N/A	ENSP00000380663.2	Q9UM01

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000801 AC: 2 AN: 249762 Hom.: 0 Cov.: 2 AF XY: 0.00000744 AC XY: 1 AN XY: 134426

African (AFR) AF: 0.00 AC: 0 AN: 7386

American (AMR) AF: 0.00 AC: 0 AN: 11948

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6934

East Asian (EAS) AF: 0.00 AC: 0 AN: 13032

South Asian (SAS) AF: 0.00 AC: 0 AN: 39996

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11112

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 966

European-Non Finnish (NFE) AF: 0.0000138 AC: 2 AN: 145042

Other (OTH) AF: 0.00 AC: 0 AN: 13346

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.39
DANN	Benign	0.73
PhyloP100		-2.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs12433985; hg19: chr14-23249539;