20-62812373-C-T

Variant summary

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

The NM_007346.4(OGFR):​c.758C>T​(p.Ala253Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000771 in 1,569,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

OGFR
NM_007346.4 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.82
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17036828).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OGFRNM_007346.4 linkc.758C>T p.Ala253Val 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.758C>T p.Ala253Val missense_variant Exon 7 of 7 1 NM_007346.4 ENSP00000290291.6 Q9NZT2-1
OGFRENST00000370461.5 linkc.602C>T p.Ala201Val missense_variant Exon 5 of 5 2 ENSP00000359491.1 A0A0A0MRN5

Frequencies

GnomAD3 genomes
AF:
0.0000591
AC:
9
AN:
152192
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.000132
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000503
AC:
9
AN:
179102
Hom.:
0
AF XY:
0.0000515
AC XY:
5
AN XY:
97018
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000362
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:
0.000108
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000790
AC:
112
AN:
1417320
Hom.:
0
Cov.:
63
AF XY:
0.0000784
AC XY:
55
AN XY:
701626
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000259
Gnomad4 ASJ exome
AF:
0.0000394
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000981
Gnomad4 OTH exome
AF:
0.0000512
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152192
Hom.:
0
Cov.:
33
AF XY:
0.0000807
AC XY:
6
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000848
Hom.:
0
Bravo
AF:
0.0000529
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000235
AC:
2
ExAC
AF:
0.0000509
AC:
6

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 13, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.758C>T (p.A253V) 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 758, causing the alanine (A) at amino acid position 253 to be replaced by a valine (V). 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
0.12
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
T;T;.
Eigen
Benign
0.15
Eigen_PC
Uncertain
0.22
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Uncertain
0.88
D;D;D
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.17
T;T;T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
1.1
L;.;.
PrimateAI
Uncertain
0.70
T
PROVEAN
Uncertain
-2.7
D;.;D
REVEL
Benign
0.17
Sift
Benign
0.14
T;.;T
Sift4G
Benign
0.094
T;T;T
Polyphen
0.48
P;.;.
Vest4
0.13
MVP
0.30
MPC
0.66
ClinPred
0.21
T
GERP RS
4.6
Varity_R
0.20
gMVP
0.52

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: rs377251680; hg19: chr20-61443725; API