chr20-7882896-A-G

Variant names:

• chr20-7882896-A-G
• rs6055363
• NM_017545.3:c.*697T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017545.3(HAO1):​c.*697T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0882 in 152,366 control chromosomes in the GnomAD database, including 1,289 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency:
  • Genomes: 𝑓 0.088 (1288 hom., cov: 33)
  • Exomes 𝑓: 0.036 (1 hom.)
• Consequence: HAO1 NM_017545.3 downstream_gene
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 0.706
• Publications: 2 publications found

Genes affected

HAO1 (HGNC:4809): (hydroxyacid oxidase 1) This gene is one of three related genes that have 2-hydroxyacid oxidase activity yet differ in encoded protein amino acid sequence, tissue expression and substrate preference. Subcellular location of the encoded protein is the peroxisome. Specifically, this gene is expressed primarily in liver and pancreas and the encoded protein is most active on glycolate, a two-carbon substrate. The protein is also active on 2-hydroxy fatty acids. The transcript detected at high levels in pancreas may represent an alternatively spliced form or the use of a multiple near-consensus upstream polyadenylation site. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017545.3. 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
	HAO1	NM_017545.3	MANE Select	c.*697T>C		downstream_gene	N/A	NP_060015.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAO1	ENST00000378789.4	TSL:1 MANE Select	c.*697T>C		downstream_gene	N/A	ENSP00000368066.3

Frequencies

GnomAD3 genomes AF: 0.0882 AC: 13418 AN: 152164 Hom.: 1286 Cov.: 33

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.0565

Gnomad FIN AF: 0.0269

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0190

Gnomad OTH AF: 0.0727

GnomAD4 exome AF: 0.0357 AC: 3 AN: 84 Hom.: 1 AF XY: 0.0400 AC XY: 2 AN XY: 50

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 2 AN: 4

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 70

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0883 AC: 13443 AN: 152282 Hom.: 1288 Cov.: 33 AF XY: 0.0906 AC XY: 6745 AN XY: 74458

African (AFR) AF: 0.184 AC: 7663 AN: 41540

American (AMR) AF: 0.105 AC: 1599 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3472

East Asian (EAS) AF: 0.405 AC: 2098 AN: 5180

South Asian (SAS) AF: 0.0570 AC: 275 AN: 4824

European-Finnish (FIN) AF: 0.0269 AC: 286 AN: 10626

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0190 AC: 1291 AN: 68022

Other (OTH) AF: 0.0728 AC: 154 AN: 2114

Alfa AF: 0.0629 Hom.: 101

Bravo AF: 0.101

Asia WGS AF: 0.209 AC: 725 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Nephrolithiasis, calcium oxalate Other:1

Mar 01, 2014

Division of Molecular Genetics and Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University

Significance: association

Review Status: no assertion criteria provided

Collection Method: case-control

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.5
DANN	Benign	0.37
PhyloP100		0.71
Mutation Taster		=93/7	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs6055363; hg19: chr20-7863543;