rs180177176

Variant names:

• chr2-240869156-C-T
• rs180177176
• NM_000030.3:c.166-14C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000030.3(AGXT):​c.166-14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00434 in 1,439,122 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (2 hom., cov: 30)
  • Exomes 𝑓: 0.0043 (24 hom.)
• Consequence: AGXT NM_000030.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts U:1 B:5
• Conservation: PhyloP100: -0.0600
• 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: 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=-0.87).
• BP6: Variant 2-240869156-C-T is Benign according to our data. Variant chr2-240869156-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 204029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00458 (497/108398) while in subpopulation NFE AF = 0.00869 (388/44660). AF 95% confidence interval is 0.00797. There are 2 homozygotes in GnomAd4. There are 252 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.166-14C>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.166-14C>T		intron	N/A	ENSP00000302620.3	P21549
	AGXT	ENST00000908235.1		c.166-14C>T		intron	N/A	ENSP00000578294.1
	AGXT	ENST00000908236.1		c.166-14C>T		intron	N/A	ENSP00000578295.1

Frequencies

GnomAD3 genomes AF: 0.00460 AC: 498 AN: 108308 Hom.: 2 Cov.: 30

Gnomad AFR AF: 0.000894

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.00126

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000505

Gnomad FIN AF: 0.00585

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00871

Gnomad OTH AF: 0.00209

GnomAD2 exomes AF: 0.00347 AC: 868 AN: 250318 AF XY: 0.00338

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.00249

Gnomad ASJ exome AF: 0.000499

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00407

Gnomad NFE exome AF: 0.00574

Gnomad OTH exome AF: 0.00394

GnomAD4 exome AF: 0.00432 AC: 5749 AN: 1330724 Hom.: 24 Cov.: 34 AF XY: 0.00428 AC XY: 2830 AN XY: 660696

African (AFR) AF: 0.000615 AC: 19 AN: 30894

American (AMR) AF: 0.00276 AC: 115 AN: 41634

Ashkenazi Jewish (ASJ) AF: 0.000896 AC: 20 AN: 22328

East Asian (EAS) AF: 0.0000277 AC: 1 AN: 36162

South Asian (SAS) AF: 0.000362 AC: 29 AN: 80062

European-Finnish (FIN) AF: 0.00551 AC: 227 AN: 41196

Middle Eastern (MID) AF: 0.00346 AC: 17 AN: 4912

European-Non Finnish (NFE) AF: 0.00506 AC: 5161 AN: 1020358

Other (OTH) AF: 0.00301 AC: 160 AN: 53178

GnomAD4 genome AF: 0.00458 AC: 497 AN: 108398 Hom.: 2 Cov.: 30 AF XY: 0.00473 AC XY: 252 AN XY: 53250

African (AFR) AF: 0.000892 AC: 29 AN: 32496

American (AMR) AF: 0.00295 AC: 35 AN: 11884

Ashkenazi Jewish (ASJ) AF: 0.00126 AC: 3 AN: 2390

East Asian (EAS) AF: 0.00 AC: 0 AN: 4518

South Asian (SAS) AF: 0.000505 AC: 2 AN: 3958

European-Finnish (FIN) AF: 0.00585 AC: 37 AN: 6322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 184

European-Non Finnish (NFE) AF: 0.00869 AC: 388 AN: 44660

Other (OTH) AF: 0.00206 AC: 3 AN: 1456

Alfa AF: 0.00329 Hom.: 2

Bravo AF: 0.00282

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.8
DANN	Benign	0.39
PhyloP100		-0.060
PromoterAI		0.021	Neutral
Mutation Taster		=100/0	polymorphism

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: rs180177176; hg19: chr2-241808573;