16-4506947-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002134.4(HMOX2):c.139C>T(p.Arg47Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,613,944 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
HMOX2
NM_002134.4 missense
NM_002134.4 missense
Scores
2
9
8
Clinical Significance
Conservation
PhyloP100: 2.41
Genes affected
HMOX2 (HGNC:5014): (heme oxygenase 2) Heme oxygenase, an essential enzyme in heme catabolism, cleaves heme to form biliverdin, which is subsequently converted to bilirubin by biliverdin reductase, and carbon monoxide, a putative neurotransmitter. Heme oxygenase activity is induced by its substrate heme and by various nonheme substances. Heme oxygenase occurs as 2 isozymes, an inducible heme oxygenase-1 and a constitutive heme oxygenase-2. HMOX1 and HMOX2 belong to the heme oxygenase family. Several alternatively spliced transcript variants encoding three different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
HMOX2 | NM_002134.4 | c.139C>T | p.Arg47Trp | missense_variant | 3/6 | ENST00000570646.6 | NP_002125.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
HMOX2 | ENST00000570646.6 | c.139C>T | p.Arg47Trp | missense_variant | 3/6 | 1 | NM_002134.4 | ENSP00000459214 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152112Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251480Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135910
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GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461832Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11AN XY: 727222
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152112Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74302
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 23, 2023 | The c.139C>T (p.R47W) alteration is located in exon 4 (coding exon 2) of the HMOX2 gene. This alteration results from a C to T substitution at nucleotide position 139, causing the arginine (R) at amino acid position 47 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
.;T;T;T;T;T;T;.;T;.;T;T;.;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;.;.;.;.;D;.;D;D;D;D;D;D;.;.;D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M;M;M;M;M;M;.;.;.;.;.;.;M;M;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
.;D;.;D;.;.;D;.;.;.;.;.;.;D;D;.
REVEL
Benign
Sift
Uncertain
.;D;.;D;.;.;D;.;.;.;.;.;.;D;D;.
Sift4G
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen
1.0
.;D;D;D;D;D;D;.;.;.;.;.;.;D;D;.
Vest4
0.24, 0.24, 0.24, 0.24, 0.24
MutPred
Loss of disorder (P = 0.0096);Loss of disorder (P = 0.0096);Loss of disorder (P = 0.0096);Loss of disorder (P = 0.0096);Loss of disorder (P = 0.0096);Loss of disorder (P = 0.0096);Loss of disorder (P = 0.0096);.;Loss of disorder (P = 0.0096);Loss of disorder (P = 0.0096);Loss of disorder (P = 0.0096);Loss of disorder (P = 0.0096);Loss of disorder (P = 0.0096);Loss of disorder (P = 0.0096);Loss of disorder (P = 0.0096);.;
MVP
MPC
0.50
ClinPred
D
GERP RS
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gMVP
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at