chr16-56470056-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_018233.4(OGFOD1):ā€‹c.954G>Cā€‹(p.Trp318Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,613,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000039 ( 0 hom., cov: 31)
Exomes š‘“: 0.000030 ( 0 hom. )

Consequence

OGFOD1
NM_018233.4 missense

Scores

10
5
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.57
Variant links:
Genes affected
OGFOD1 (HGNC:25585): (2-oxoglutarate and iron dependent oxygenase domain containing 1) Enables peptidyl-proline 3-dioxygenase activity. Involved in several processes, including peptidyl-proline hydroxylation; regulation of translational termination; and stress granule assembly. Located in cytoplasmic stress granule; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
BBS2 (HGNC:967): (Bardet-Biedl syndrome 2) This gene is a member of the Bardet-Biedl syndrome (BBS) gene family. Bardet-Biedl syndrome is an autosomal recessive disorder characterized by severe pigmentary retinopathy, obesity, polydactyly, renal malformation and cognitive disability. The proteins encoded by BBS gene family members are structurally diverse and the similar phenotypes exhibited by mutations in BBS gene family members is likely due to their shared roles in cilia formation and function. Many BBS proteins localize to the basal bodies, ciliary axonemes, and pericentriolar regions of cells. BBS proteins may also be involved in intracellular trafficking via microtubule-related transport. The protein encoded by this gene forms a multiprotein BBSome complex with seven other BBS proteins.[provided by RefSeq, Oct 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.872

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OGFOD1NM_018233.4 linkuse as main transcriptc.954G>C p.Trp318Cys missense_variant 9/13 ENST00000566157.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OGFOD1ENST00000566157.6 linkuse as main transcriptc.954G>C p.Trp318Cys missense_variant 9/131 NM_018233.4 P1Q8N543-1

Frequencies

GnomAD3 genomes
AF:
0.0000395
AC:
6
AN:
152074
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000278
AC:
7
AN:
251460
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135902
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:
0.0000615
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000301
AC:
44
AN:
1461874
Hom.:
0
Cov.:
31
AF XY:
0.0000316
AC XY:
23
AN XY:
727240
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000369
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000395
AC:
6
AN:
152074
Hom.:
0
Cov.:
31
AF XY:
0.0000404
AC XY:
3
AN XY:
74300
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000149
Hom.:
0
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

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 GeneticsMar 01, 2023The c.954G>C (p.W318C) alteration is located in exon 9 (coding exon 9) of the OGFOD1 gene. This alteration results from a G to C substitution at nucleotide position 954, causing the tryptophan (W) at amino acid position 318 to be replaced by a cysteine (C). 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
Pathogenic
0.94
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Pathogenic
0.25
CADD
Pathogenic
31
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.53
D;T
Eigen
Pathogenic
0.96
Eigen_PC
Pathogenic
0.93
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Benign
0.85
D;D
M_CAP
Benign
0.053
D
MetaRNN
Pathogenic
0.87
D;D
MetaSVM
Uncertain
0.11
D
MutationAssessor
Pathogenic
3.3
M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.54
T
PROVEAN
Pathogenic
-10
D;D
Sift
Uncertain
0.0010
D;D
Sift4G
Pathogenic
0.0010
D;D
Polyphen
1.0
D;.
Vest4
0.87
MutPred
0.67
Gain of catalytic residue at S320 (P = 0.0412);.;
MVP
0.89
MPC
0.72
ClinPred
1.0
D
GERP RS
6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.93
gMVP
0.91

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs757643773; hg19: chr16-56503968; API