rs34995778

Variant names:

• chr2-240869375-C-T
• rs34995778
• NM_000030.3:c.358+13C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-240869375-C-T
• chr2-240869375-C-A
• chr2-240869375-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000030.3(AGXT):​c.358+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,565,884 control chromosomes in the GnomAD database, including 28,390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1989 hom., cov: 33)
  • Exomes 𝑓: 0.19 (26401 hom.)
• Consequence: AGXT NM_000030.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:6
• Conservation: PhyloP100: -0.839
• Publications: 6 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-240869375-C-T is Benign according to our data. Variant chr2-240869375-C-T is described in ClinVar as Benign. ClinVar VariationId is 204032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

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.358+13C>T		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.358+13C>T		intron	N/A	ENSP00000302620.3	P21549
	AGXT	ENST00000908235.1		c.358+13C>T		intron	N/A	ENSP00000578294.1
	AGXT	ENST00000908236.1		c.358+13C>T		intron	N/A	ENSP00000578295.1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22025 AN: 151678 Hom.: 1986 Cov.: 33

Gnomad AFR AF: 0.0627

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.000967

Gnomad SAS AF: 0.0732

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.162

GnomAD2 exomes AF: 0.146 AC: 30732 AN: 210064 AF XY: 0.150

Gnomad AFR exome AF: 0.0629

Gnomad AMR exome AF: 0.0820

Gnomad ASJ exome AF: 0.188

Gnomad EAS exome AF: 0.000334

Gnomad FIN exome AF: 0.247

Gnomad NFE exome AF: 0.203

Gnomad OTH exome AF: 0.173

GnomAD4 exome AF: 0.185 AC: 261660 AN: 1414088 Hom.: 26401 Cov.: 33 AF XY: 0.182 AC XY: 127017 AN XY: 696968

African (AFR) AF: 0.0642 AC: 2097 AN: 32654

American (AMR) AF: 0.0835 AC: 3475 AN: 41620

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 4050 AN: 22894

East Asian (EAS) AF: 0.000331 AC: 13 AN: 39276

South Asian (SAS) AF: 0.0755 AC: 5900 AN: 78172

European-Finnish (FIN) AF: 0.233 AC: 11589 AN: 49834

Middle Eastern (MID) AF: 0.165 AC: 868 AN: 5246

European-Non Finnish (NFE) AF: 0.206 AC: 223804 AN: 1086078

Other (OTH) AF: 0.169 AC: 9864 AN: 58314

GnomAD4 genome AF: 0.145 AC: 22030 AN: 151796 Hom.: 1989 Cov.: 33 AF XY: 0.143 AC XY: 10617 AN XY: 74176

African (AFR) AF: 0.0627 AC: 2604 AN: 41520

American (AMR) AF: 0.119 AC: 1823 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 619 AN: 3468

East Asian (EAS) AF: 0.000969 AC: 5 AN: 5158

South Asian (SAS) AF: 0.0741 AC: 354 AN: 4778

European-Finnish (FIN) AF: 0.231 AC: 2426 AN: 10500

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13604 AN: 67818

Other (OTH) AF: 0.159 AC: 333 AN: 2090

Alfa AF: 0.169 Hom.: 478

Bravo AF: 0.135

Asia WGS AF: 0.0330 AC: 116 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	1	2	Primary hyperoxaluria, type I (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.86
DANN	Benign	0.66
PhyloP100		-0.84
Mutation Taster		=100/0	polymorphism (auto)

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: rs34995778; hg19: chr2-241808792; COSMIC: COSV56755317; COSMIC: COSV56755317;