rs180177174

Variant names:

• chr2-240869043-G-GTCACTCGGGGGGCCTGGGTCTCACCCATGTTCCCACCCACAGATCGTGGACGAGGGAAGGGGGTCACTGCCTCC
• rs180177174
• NM_000030.3:c.165+19_166-48dupCGGGGGGCCTGGGTCTCACCCATGTTCCCACCCACAGATCGTGGACGAGGGAAGGGGGTCACTGCCTCCTCACT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_000030.3(AGXT):​c.165+19_166-48dupCGGGGGGCCTGGGTCTCACCCATGTTCCCACCCACAGATCGTGGACGAGGGAAGGGGGTCACTGCCTCCTCACT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: AGXT NM_000030.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: -1.53
• Publications: 2 publications found

Genes affected

AGXT (HGNC:341): (alanine--glyoxylate aminotransferase) This gene is expressed only in the liver and the encoded protein is localized mostly in the peroxisomes, where it is involved in glyoxylate detoxification. Mutations in this gene, some of which alter subcellular targetting, have been associated with type I primary hyperoxaluria. [provided by RefSeq, Jul 2008]

AGXT Gene-Disease associations (from GenCC):

• alanine glyoxylate aminotransferase deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• primary hyperoxaluria type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Orphanet, Labcorp Genetics (formerly Invitae), Myriad Women’s Health

ENSG00000297735 (HGNC:):

ACMG classification

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

• BP6: Variant 2-240869043-G-GTCACTCGGGGGGCCTGGGTCTCACCCATGTTCCCACCCACAGATCGTGGACGAGGGAAGGGGGTCACTGCCTCC is Benign according to our data. Variant chr2-240869043-G-GTCACTCGGGGGGCCTGGGTCTCACCCATGTTCCCACCCACAGATCGTGGACGAGGGAAGGGGGTCACTGCCTCC is described in ClinVar as Likely_benign. ClinVar VariationId is 204024.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000030.3. 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
	AGXT	NM_000030.3	MANE Select	c.165+19_166-48dupCGGGGGGCCTGGGTCTCACCCATGTTCCCACCCACAGATCGTGGACGAGGGAAGGGGGTCACTGCCTCCTCACT		intron	N/A	NP_000021.1	P21549

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGXT	ENST00000307503.4	TSL:1 MANE Select	c.165+13_165+14insTCACTCGGGGGGCCTGGGTCTCACCCATGTTCCCACCCACAGATCGTGGACGAGGGAAGGGGGTCACTGCCTCC		intron	N/A	ENSP00000302620.3	P21549
	AGXT	ENST00000908235.1		c.165+13_165+14insTCACTCGGGGGGCCTGGGTCTCACCCATGTTCCCACCCACAGATCGTGGACGAGGGAAGGGGGTCACTGCCTCC		intron	N/A	ENSP00000578294.1
	AGXT	ENST00000908236.1		c.165+13_165+14insTCACTCGGGGGGCCTGGGTCTCACCCATGTTCCCACCCACAGATCGTGGACGAGGGAAGGGGGTCACTGCCTCC		intron	N/A	ENSP00000578295.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	1	-	Primary hyperoxaluria, type I (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs180177174; hg19: chr2-241808460;