20-62812307-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007346.4(OGFR):​c.692C>T​(p.Pro231Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000428 in 1,401,340 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

OGFR
NM_007346.4 missense

Scores

3
10
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.18
Variant links:
Genes affected
OGFR (HGNC:15768): (opioid growth factor receptor) The protein encoded by this gene is a receptor for opioid growth factor (OGF), also known as [Met(5)]-enkephalin. OGF is a negative regulator of cell proliferation and tissue organization in a variety of processes. The encoded unbound receptor for OGF has been localized to the outer nuclear envelope, where it binds OGF and is translocated into the nucleus. The coding sequence of this gene contains a polymorphic region of 60 nt tandem imperfect repeat units. Several transcripts containing between zero and eight repeat units have been reported. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

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 rank MANE Protein UniProt
OGFRNM_007346.4 linkc.692C>T p.Pro231Leu missense_variant Exon 7 of 7 ENST00000290291.10 NP_031372.2 Q9NZT2-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OGFRENST00000290291.10 linkc.692C>T p.Pro231Leu missense_variant Exon 7 of 7 1 NM_007346.4 ENSP00000290291.6 Q9NZT2-1
OGFRENST00000370461.5 linkc.536C>T p.Pro179Leu missense_variant Exon 5 of 5 2 ENSP00000359491.1 A0A0A0MRN5

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
0.00000428
AC:
6
AN:
1401340
Hom.:
0
Cov.:
50
AF XY:
0.00000434
AC XY:
3
AN XY:
691884
show subpopulations
Gnomad4 AFR exome
AF:
0.0000315
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000370
Gnomad4 OTH exome
AF:
0.0000172
GnomAD4 genome
Cov.:
34
Bravo
AF:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 28, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.692C>T (p.P231L) alteration is located in exon 7 (coding exon 7) of the OGFR gene. This alteration results from a C to T substitution at nucleotide position 692, causing the proline (P) at amino acid position 231 to be replaced by a leucine (L). 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
0.71
BayesDel_addAF
Uncertain
0.064
T
BayesDel_noAF
Benign
-0.15
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
T;T;.
Eigen
Uncertain
0.38
Eigen_PC
Benign
0.22
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Uncertain
0.95
D;D;D
M_CAP
Uncertain
0.089
D
MetaRNN
Uncertain
0.74
D;D;D
MetaSVM
Benign
-0.46
T
MutationAssessor
Pathogenic
3.0
M;.;.
PrimateAI
Uncertain
0.63
T
PROVEAN
Pathogenic
-8.6
D;.;D
REVEL
Uncertain
0.37
Sift
Uncertain
0.0030
D;.;D
Sift4G
Benign
0.073
T;D;D
Polyphen
1.0
D;.;.
Vest4
0.68
MutPred
0.74
Gain of loop (P = 0.024);Gain of loop (P = 0.024);.;
MVP
0.60
MPC
0.99
ClinPred
0.99
D
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.48
gMVP
0.77

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: rs1281729415; hg19: chr20-61443659; API