NM_000341.4:c.1275_1276dupTG

Variant names:

• chr2-44304280-A-ATG
• rs797044609
• NM_000341.4:c.1275_1276dupTG

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_000341.4(SLC3A1):​c.1275_1276dupTG​(p.Glu426ValfsTer20) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC3A1 NM_000341.4 frameshift
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.379
• Publications: 0 publications found

Genes affected

SLC3A1 (HGNC:11025): (solute carrier family 3 member 1) This gene encodes a type II membrane glycoprotein which is one of the components of the renal amino acid transporter which transports neutral and basic amino acids in the renal tubule and intestinal tract. Mutations and deletions in this gene are associated with cystinuria. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

SLC3A1 Gene-Disease associations (from GenCC):

• cystinuria

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• cystinuria type A

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285542 (HGNC:):

ACMG classification

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 2-44304280-A-ATG is Pathogenic according to our data. Variant chr2-44304280-A-ATG is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 212741.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000341.4. 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
	SLC3A1	NM_000341.4	MANE Select	c.1275_1276dupTG	p.Glu426ValfsTer20	frameshift	Exon 7 of 10	NP_000332.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC3A1	ENST00000260649.11	TSL:1 MANE Select	c.1275_1276dupTG	p.Glu426ValfsTer20	frameshift	Exon 7 of 10	ENSP00000260649.6
	SLC3A1	ENST00000409229.7	TSL:1	c.1275_1276dupTG	p.Glu426ValfsTer20	frameshift	Exon 7 of 9	ENSP00000386620.3
	SLC3A1	ENST00000409387.5	TSL:1	c.1275_1276dupTG	p.Glu426ValfsTer20	frameshift	Exon 7 of 10	ENSP00000387308.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Likely pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Cystinuria (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.38

Splicing

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

Other links and lift over

dbSNP: rs797044609; hg19: chr2-44531419;