6-71301607-C-T

Variant summary

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

The NM_024576.5(OGFRL1):​c.914C>T​(p.Thr305Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000291 in 1,614,042 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

OGFRL1
NM_024576.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.348
Variant links:
Genes affected
OGFRL1 (HGNC:21378): (opioid growth factor receptor like 1) Predicted to enable opioid growth factor receptor activity. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Apr 2022]
LINC00472 (HGNC:21380): (long intergenic non-protein coding RNA 472)

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=0.14214507).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OGFRL1NM_024576.5 linkc.914C>T p.Thr305Met missense_variant Exon 7 of 7 ENST00000370435.5 NP_078852.3 Q5TC84

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OGFRL1ENST00000370435.5 linkc.914C>T p.Thr305Met missense_variant Exon 7 of 7 1 NM_024576.5 ENSP00000359464.3 Q5TC84

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152170
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000558
AC:
14
AN:
251084
Hom.:
0
AF XY:
0.0000737
AC XY:
10
AN XY:
135756
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:
0.000359
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000294
AC:
43
AN:
1461872
Hom.:
0
Cov.:
32
AF XY:
0.0000316
AC XY:
23
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000174
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000162
Gnomad4 OTH exome
AF:
0.000132
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152170
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.0000483
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.0000340
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000494
AC:
6
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 17, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.914C>T (p.T305M) alteration is located in exon 7 (coding exon 7) of the OGFRL1 gene. This alteration results from a C to T substitution at nucleotide position 914, causing the threonine (T) at amino acid position 305 to be replaced by a methionine (M). 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
0.071
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.066
T;.
Eigen
Benign
-0.14
Eigen_PC
Benign
-0.19
FATHMM_MKL
Benign
0.16
N
LIST_S2
Benign
0.73
T;T
M_CAP
Benign
0.031
D
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.0
L;.
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-1.8
N;.
REVEL
Benign
0.10
Sift
Benign
0.093
T;.
Sift4G
Benign
0.080
T;.
Polyphen
1.0
D;.
Vest4
0.32
MVP
0.25
MPC
0.91
ClinPred
0.20
T
GERP RS
2.1
Varity_R
0.022
gMVP
0.27

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: rs373599406; hg19: chr6-72011310; COSMIC: COSV64972293; COSMIC: COSV64972293; API