12-122978808-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001304833.2(OGFOD2):​c.587G>A​(p.Arg196His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,459,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

OGFOD2
NM_001304833.2 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.77
Variant links:
Genes affected
OGFOD2 (HGNC:25823): (2-oxoglutarate and iron dependent oxygenase domain containing 2) Predicted to enable several functions, including L-ascorbic acid binding activity; dioxygenase activity; and iron ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]
ABCB9 (HGNC:50): (ATP binding cassette subfamily B member 9) The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance as well as antigen presentation. This family member functions in the translocation of peptides from the cytosol into the lysosomal lumen. Alternative splicing of this gene results in distinct isoforms which are likely to have different substrate specificities. [provided by RefSeq, Jul 2011]

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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=0.2299121).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OGFOD2NM_001304833.2 linkuse as main transcriptc.587G>A p.Arg196His missense_variant 6/7 ENST00000228922.12 NP_001291762.1 Q6N063-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OGFOD2ENST00000228922.12 linkuse as main transcriptc.587G>A p.Arg196His missense_variant 6/71 NM_001304833.2 ENSP00000228922.7 Q6N063-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000123
AC:
3
AN:
244324
Hom.:
0
AF XY:
0.0000150
AC XY:
2
AN XY:
133776
show subpopulations
Gnomad AFR exome
AF:
0.0000676
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000328
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000909
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000753
AC:
11
AN:
1459890
Hom.:
0
Cov.:
31
AF XY:
0.00000551
AC XY:
4
AN XY:
726260
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
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:
0.00000720
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.00000828
AC:
1

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 submitterclinical testingAmbry GeneticsJul 14, 2024The c.407G>A (p.R136H) alteration is located in exon 7 (coding exon 5) of the OGFOD2 gene. This alteration results from a G to A substitution at nucleotide position 407, causing the arginine (R) at amino acid position 136 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.067
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.31
CADD
Benign
18
DANN
Uncertain
0.99
DEOGEN2
Benign
0.029
.;.;.;T;.;.;.;.;T;T
Eigen
Benign
-0.32
Eigen_PC
Benign
-0.24
FATHMM_MKL
Benign
0.66
D
LIST_S2
Uncertain
0.89
D;.;.;.;.;.;.;D;D;D
M_CAP
Uncertain
0.091
D
MetaRNN
Benign
0.23
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.49
T
MutationAssessor
Benign
0.72
.;.;.;.;.;.;.;.;N;.
PrimateAI
Benign
0.33
T
PROVEAN
Benign
-0.68
N;N;N;N;N;N;N;N;N;N
REVEL
Benign
0.063
Sift
Benign
0.28
T;T;T;T;T;T;T;T;T;T
Sift4G
Benign
0.30
T;T;T;T;T;T;T;T;T;T
Polyphen
0.0080
B;.;.;.;.;.;.;.;B;.
Vest4
0.24
MutPred
0.29
.;.;.;.;.;.;.;.;Gain of catalytic residue at L198 (P = 0.066);.;
MVP
0.83
MPC
0.042
ClinPred
0.040
T
GERP RS
1.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.029
gMVP
0.60

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs748715296; hg19: chr12-123463355; API