rs10196315

Variant names:

• chr2-240871540-C-A
• rs10196315
• NM_000030.3:c.524+91C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-240871540-C-A
• chr2-240871540-C-T

Variant summary

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

The NM_000030.3(AGXT):​c.524+91C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000095 in 1,053,154 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: 33)
  • Exomes 𝑓: 9.5e-7 (0 hom.)
• Consequence: AGXT NM_000030.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.601
• Publications: 4 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

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=-0.82).

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.524+91C>A		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.524+91C>A		intron	N/A	ENSP00000302620.3
	AGXT	ENST00000472436.1	TSL:2	n.544+91C>A		intron	N/A
	AGXT	ENST00000476698.1	TSL:5	n.261+91C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.50e-7 AC: 1 AN: 1053154 Hom.: 0 AF XY: 0.00000188 AC XY: 1 AN XY: 532028

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

African (AFR) AF: 0.00 AC: 0 AN: 24948

American (AMR) AF: 0.00 AC: 0 AN: 35128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22944

East Asian (EAS) AF: 0.00 AC: 0 AN: 34034

South Asian (SAS) AF: 0.00 AC: 0 AN: 72454

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37888

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3910

European-Non Finnish (NFE) AF: 0.00000129 AC: 1 AN: 775172

Other (OTH) AF: 0.00 AC: 0 AN: 46676

⚠️ 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 Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.3
DANN	Benign	0.66
PhyloP100		-0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs10196315; hg19: chr2-241810957;