dbSNP rs140054426: HAO2:p.Thr197Asn (chr1-119386650-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_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. 15/21 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.86

Variant links:

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]

HAO2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10476494).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HAO2	NM_016527.4 link	c.590C>A	p.Thr197Asn	missense_variant	Exon 5 of 8	ENST00000325945.4	NP_057611.1	Q9NYQ3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
HAO2	ENST00000325945.4 link	c.590C>A	p.Thr197Asn	missense_variant	Exon 5 of 8	1	NM_016527.4	ENSP00000316339.3	Q9NYQ3-1
HAO2	ENST00000361035.8 link	c.629C>A	p.Thr210Asn	missense_variant	Exon 6 of 9	1		ENSP00000354314.4	Q9NYQ3-2
HAO2	ENST00000622548.4 link	c.590C>A	p.Thr197Asn	missense_variant	Exon 6 of 9	1		ENSP00000483507.1	Q9NYQ3-1
HAO2	ENST00000457318.5 link	c.515C>A	p.Thr172Asn	missense_variant	Exon 5 of 5	3		ENSP00000393955.1	Q5QP02

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250616

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135414

show subpopulations

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 SAS exome

AF:

0.0000327

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:

AN:

1458414

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725780

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.68

CADD

Benign

6.0

DANN

Benign

0.69

DEOGEN2

Benign

0.0039

T;T;.;T

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.64

T;T;T;.

M_CAP

Benign

0.0052

MetaRNN

Benign

0.10

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.23

.;N;.;N

PrimateAI

Benign

0.27

PROVEAN

Benign

0.37

N;.;N;N

REVEL

Benign

0.11

Sift

Benign

0.38

T;.;T;T

Sift4G

Benign

0.50

T;T;T;T

Polyphen

0.0

.;B;.;B

Vest4

0.13, 0.13, 0.12

MutPred

0.40

.;Loss of sheet (P = 0.0315);.;Loss of sheet (P = 0.0315);

MVP

0.34

MPC

0.027

ClinPred

0.040

GERP RS

4.2

Varity_R

0.044

gMVP

0.39

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over