chr2-240869123-T-C

Variant names:

• chr2-240869123-T-C
• rs180177178
• NM_000030.3:c.166-47T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000030.3(AGXT):​c.166-47T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000050 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AGXT NM_000030.3 intron
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: -4.09
• Publications: 0 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: G2P, Myriad Women’s Health, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000297735 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGXT	NM_000030.3	MANE Select	c.166-47T>C		intron	N/A	NP_000021.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGXT	ENST00000307503.4	TSL:1 MANE Select	c.166-47T>C		intron	N/A	ENSP00000302620.3
	AGXT	ENST00000472436.1	TSL:2	n.186-47T>C		intron	N/A
	ENSG00000297735	ENST00000750632.1		n.237+1110A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000660 AC: 7 AN: 106034 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000639

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000852

Gnomad ASJ AF: 0.000424

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000258

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000456

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000480 AC: 10 AN: 208438 AF XY: 0.0000445

Gnomad AFR exome AF: 0.000136

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000122

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000580

Gnomad NFE exome AF: 0.0000691

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000499 AC: 53 AN: 1062480 Hom.: 0 Cov.: 31 AF XY: 0.0000412 AC XY: 22 AN XY: 533436

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000360 AC: 1 AN: 27758

American (AMR) AF: 0.00 AC: 0 AN: 39442

Ashkenazi Jewish (ASJ) AF: 0.0000498 AC: 1 AN: 20076

East Asian (EAS) AF: 0.00 AC: 0 AN: 35420

South Asian (SAS) AF: 0.00 AC: 0 AN: 76612

European-Finnish (FIN) AF: 0.0000535 AC: 2 AN: 37368

Middle Eastern (MID) AF: 0.000228 AC: 1 AN: 4386

European-Non Finnish (NFE) AF: 0.0000618 AC: 48 AN: 776080

Other (OTH) AF: 0.00 AC: 0 AN: 45338

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000660 AC: 7 AN: 106034 Hom.: 0 Cov.: 29 AF XY: 0.0000384 AC XY: 2 AN XY: 52050

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000639 AC: 2 AN: 31314

American (AMR) AF: 0.0000852 AC: 1 AN: 11740

Ashkenazi Jewish (ASJ) AF: 0.000424 AC: 1 AN: 2358

East Asian (EAS) AF: 0.00 AC: 0 AN: 4442

South Asian (SAS) AF: 0.000258 AC: 1 AN: 3882

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 192

European-Non Finnish (NFE) AF: 0.0000456 AC: 2 AN: 43896

Other (OTH) AF: 0.00 AC: 0 AN: 1414

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Primary hyperoxaluria, type I (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.62
PhyloP100		-4.1
PromoterAI		0.0058	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs180177178; hg19: chr2-241808540;