1-119386650-C-A

Variant names:

• chr1-119386650-C-A
• rs140054426
• NM_016527.4:c.590C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016527.4(HAO2):​c.590C>A​(p.Thr197Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T197I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: HAO2 NM_016527.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.86
• Publications: 3 publications found

Genes affected

HAO2 (HGNC:4810): (hydroxyacid oxidase 2) This gene is one of three related genes that have 2-hydroxyacid oxidase activity. The encoded protein localizes to the peroxisome has the highest activity toward the substrate 2-hydroxypalmitate. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10476494).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016527.4. 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
	HAO2	NM_016527.4	MANE Select	c.590C>A	p.Thr197Asn	missense	Exon 5 of 8	NP_057611.1	Q9NYQ3-1
	HAO2	NM_001005783.3		c.629C>A	p.Thr210Asn	missense	Exon 6 of 9	NP_001005783.2	Q9NYQ3-2
	HAO2	NM_001377472.1		c.600+1597C>A		intron	N/A	NP_001364401.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAO2	ENST00000325945.4	TSL:1 MANE Select	c.590C>A	p.Thr197Asn	missense	Exon 5 of 8	ENSP00000316339.3	Q9NYQ3-1
	HAO2	ENST00000361035.8	TSL:1	c.629C>A	p.Thr210Asn	missense	Exon 6 of 9	ENSP00000354314.4	Q9NYQ3-2
	HAO2	ENST00000622548.4	TSL:1	c.590C>A	p.Thr197Asn	missense	Exon 6 of 9	ENSP00000483507.1	Q9NYQ3-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250616 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458414 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 725780

African (AFR) AF: 0.00 AC: 0 AN: 33410

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108924

Other (OTH) AF: 0.00 AC: 0 AN: 60280

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.0
DANN	Benign	0.69
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.23	N
PhyloP100		2.9
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.37	N
REVEL	Benign	0.11
Sift	Benign	0.38	T
Sift4G	Benign	0.50	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.40		Loss of sheet (P = 0.0315)
MVP		0.34
MPC		0.027
ClinPred		0.040	T
GERP RS		4.2
Varity_R		0.044
gMVP		0.39
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs140054426; hg19: chr1-119929273;