chr6-71301699-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.1006C>T​(p.His336Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

OGFRL1
NM_024576.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.46
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)

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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=0.09481308).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OGFRL1NM_024576.5 linkc.1006C>T p.His336Tyr 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.1006C>T p.His336Tyr missense_variant Exon 7 of 7 1 NM_024576.5 ENSP00000359464.3 Q5TC84

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 26, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1006C>T (p.H336Y) 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 1006, causing the histidine (H) at amino acid position 336 to be replaced by a tyrosine (Y). 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
0.081
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
19
DANN
Benign
0.74
DEOGEN2
Benign
0.034
T;.
Eigen
Benign
-0.53
Eigen_PC
Benign
-0.55
FATHMM_MKL
Benign
0.32
N
LIST_S2
Benign
0.72
T;T
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.095
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
L;.
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-2.2
N;.
REVEL
Benign
0.081
Sift
Benign
0.081
T;.
Sift4G
Uncertain
0.041
D;.
Polyphen
0.75
P;.
Vest4
0.17
MutPred
0.16
Gain of phosphorylation at H336 (P = 0.0168);.;
MVP
0.14
MPC
0.63
ClinPred
0.17
T
GERP RS
5.2
Varity_R
0.039
gMVP
0.26

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: rs1766396240; hg19: chr6-72011402; API