16-56467267-C-A

Position:

chr16-56467267-C-A

Variant summary

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

The NM_018233.4(OGFOD1):c.760C>A(p.Pro254Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000266 in 1,614,014 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00026 ( 1 hom. )

Consequence

OGFOD1
NM_018233.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.55

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]

OGFOD1 links:

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]

BBS2 links:

Genome browser will be placed here

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=0.07700822).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OGFOD1	NM_018233.4 linkuse as main transcript	c.760C>A	p.Pro254Thr	missense_variant	7/13	ENST00000566157.6	NP_060703.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OGFOD1	ENST00000566157.6 linkuse as main transcript	c.760C>A	p.Pro254Thr	missense_variant	7/13	1	NM_018233.4	ENSP00000457258	P1	Q8N543-1

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000290

AC:

AN:

251420

Hom.:

AF XY:

0.000309

AC XY:

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000572

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000263

AC:

385

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000285

AC XY:

207

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000393

Gnomad4 NFE exome

AF:

0.000308

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.000289

AC:

AN:

152130

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000573

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000432

Hom.:

Bravo

AF:

0.000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000412

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000296

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

Aug 02, 2023

The c.760C>A (p.P254T) alteration is located in exon 7 (coding exon 7) of the OGFOD1 gene. This alteration results from a C to A substitution at nucleotide position 760, causing the proline (P) at amino acid position 254 to be replaced by a threonine (T). 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

0.076

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.028

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.80

M_CAP

Benign

0.017

MetaRNN

Benign

0.077

MetaSVM

Benign

-0.64

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.7

Sift

Benign

0.20

Sift4G

Benign

0.60

Polyphen

0.034

Vest4

0.27

MVP

0.56

MPC

0.16

ClinPred

0.030

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.22

gMVP

0.43

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over