chr1-119381178-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_016527.4(HAO2):​c.93C>G​(p.Asp31Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000453 in 1,610,016 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000048 ( 0 hom. )

Consequence

HAO2
NM_016527.4 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.44
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0785152).
BP6
Variant 1-119381178-C-G is Benign according to our data. Variant chr1-119381178-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3856736.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HAO2NM_016527.4 linkc.93C>G p.Asp31Glu missense_variant Exon 2 of 8 ENST00000325945.4 NP_057611.1 Q9NYQ3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HAO2ENST00000325945.4 linkc.93C>G p.Asp31Glu missense_variant Exon 2 of 8 1 NM_016527.4 ENSP00000316339.3 Q9NYQ3-1
HAO2ENST00000361035.8 linkc.132C>G p.Asp44Glu missense_variant Exon 3 of 9 1 ENSP00000354314.4 Q9NYQ3-2
HAO2ENST00000622548.4 linkc.93C>G p.Asp31Glu missense_variant Exon 3 of 9 1 ENSP00000483507.1 Q9NYQ3-1
HAO2ENST00000457318.5 linkc.93C>G p.Asp31Glu missense_variant Exon 2 of 5 3 ENSP00000393955.1 Q5QP02

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152184
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251210
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135762
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.0000480
AC:
70
AN:
1457832
Hom.:
0
Cov.:
29
AF XY:
0.0000455
AC XY:
33
AN XY:
725570
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:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000550
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152184
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000312
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Feb 27, 2025
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
0.0020
DANN
Benign
0.67
DEOGEN2
Benign
0.019
T;T;.;T
Eigen
Benign
-2.0
Eigen_PC
Benign
-2.1
FATHMM_MKL
Benign
0.032
N
LIST_S2
Benign
0.72
T;T;T;.
M_CAP
Benign
0.0020
T
MetaRNN
Benign
0.079
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.66
.;N;.;N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-1.2
N;.;N;N
REVEL
Benign
0.055
Sift
Benign
0.42
T;.;T;T
Sift4G
Benign
0.72
T;T;T;T
Polyphen
0.0
.;B;.;B
Vest4
0.21, 0.22, 0.15
MutPred
0.61
Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);.;Loss of helix (P = 0.1706);
MVP
0.34
MPC
0.024
ClinPred
0.048
T
GERP RS
-10
Varity_R
0.031
gMVP
0.46

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.

Other links and lift over

dbSNP: rs775550007; hg19: chr1-119923801; API