1-119385006-C-A

Variant names:

• chr1-119385006-C-A
• rs750423937
• NM_016527.4:c.514C>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.514C>A​(p.Gln172Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,578 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: HAO2 NM_016527.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.12
• Publications: 0 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=0.08140358).

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.514C>A	p.Gln172Lys	missense	Exon 4 of 8	NP_057611.1	Q9NYQ3-1
	HAO2	NM_001005783.3		c.553C>A	p.Gln185Lys	missense	Exon 5 of 9	NP_001005783.2	Q9NYQ3-2
	HAO2	NM_001377472.1		c.553C>A	p.Gln185Lys	missense	Exon 5 of 8	NP_001364401.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAO2	ENST00000325945.4	TSL:1 MANE Select	c.514C>A	p.Gln172Lys	missense	Exon 4 of 8	ENSP00000316339.3	Q9NYQ3-1
	HAO2	ENST00000361035.8	TSL:1	c.553C>A	p.Gln185Lys	missense	Exon 5 of 9	ENSP00000354314.4	Q9NYQ3-2
	HAO2	ENST00000622548.4	TSL:1	c.514C>A	p.Gln172Lys	missense	Exon 5 of 9	ENSP00000483507.1	Q9NYQ3-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000798 AC: 2 AN: 250478 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461578 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727096

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.0000224 AC: 1 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39638

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

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

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111840

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.2
DANN	Benign	0.23
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.83	N
PhyloP100		1.1
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.54	N
REVEL	Benign	0.047
Sift	Benign	0.72	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.18
MutPred		0.57		Gain of MoRF binding (P = 0.0279)
MVP		0.33
MPC		0.028
ClinPred		0.029	T
GERP RS		0.43
Varity_R		0.16
gMVP		0.69
Mutation Taster		=92/8	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: rs750423937; hg19: chr1-119927629;