NM_014270.5:c.1428_1431dupAATG

Variant names:

• chr19-32830652-C-CCATT
• rs886042228
• NM_014270.5:c.1428_1431dupAATG

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_014270.5(SLC7A9):​c.1428_1431dupAATG​(p.Glu478AsnfsTer11) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,762 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC7A9 NM_014270.5 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.33
• Publications: 0 publications found

Genes affected

SLC7A9 (HGNC:11067): (solute carrier family 7 member 9) This gene encodes a protein that belongs to a family of light subunits of amino acid transporters. This protein plays a role in the high-affinity and sodium-independent transport of cystine and neutral and dibasic amino acids, and appears to function in the reabsorption of cystine in the kidney tubule. Mutations in this gene cause non-type I cystinuria, a disease that leads to cystine stones in the urinary system due to impaired transport of cystine and dibasic amino acids. Alternate transcript variants, which encode the same protein, have been found for this gene. [provided by RefSeq, Jul 2011]

SLC7A9 Gene-Disease associations (from GenCC):

• cystinuria

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, ClinGen
• cystinuria type B

  Inheritance: SD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0225 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014270.5. 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
	SLC7A9	NM_014270.5	MANE Select	c.1428_1431dupAATG	p.Glu478AsnfsTer11	frameshift	Exon 13 of 13	NP_055085.1	P82251
	SLC7A9	NM_001126335.2		c.1428_1431dupAATG	p.Glu478AsnfsTer11	frameshift	Exon 13 of 13	NP_001119807.1	P82251
	SLC7A9	NM_001243036.2		c.1428_1431dupAATG	p.Glu478AsnfsTer11	frameshift	Exon 13 of 13	NP_001229965.1	P82251

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC7A9	ENST00000023064.9	TSL:1 MANE Select	c.1428_1431dupAATG	p.Glu478AsnfsTer11	frameshift	Exon 13 of 13	ENSP00000023064.3	P82251
	SLC7A9	ENST00000587772.1	TSL:1	c.1428_1431dupAATG	p.Glu478AsnfsTer11	frameshift	Exon 13 of 13	ENSP00000468439.1	P82251
	SLC7A9	ENST00000590341.5	TSL:1	c.1428_1431dupAATG	p.Glu478AsnfsTer11	frameshift	Exon 13 of 13	ENSP00000464822.1	P82251

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461762 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727190

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111906

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.3

Splicing

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

Other links and lift over

dbSNP: rs886042228; hg19: chr19-33321558;