Genetic Variant NM_007346.4:c.692C>T (chr20-62812307-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.18

Publications

0 publications found

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]

OGFR links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 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
OGFR	NM_007346.4 link	c.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
OGFR	ENST00000290291.10 link	c.692C>T	p.Pro231Leu	missense_variant	Exon 7 of 7	1	NM_007346.4	ENSP00000290291.6		Q9NZT2-1
OGFR	ENST00000370461.5 link	c.536C>T	p.Pro179Leu	missense_variant	Exon 5 of 5	2		ENSP00000359491.1		A0A0A0MRN5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000428

AC:

AN:

1401340

Hom.:

Cov.:

AF XY:

0.00000434

AC XY:

AN XY:

691884

show subpopulations

African (AFR)

AF:

0.0000315

AC:

AN:

31770

American (AMR)

AF:

0.00

AC:

AN:

36132

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25092

East Asian (EAS)

AF:

0.00

AC:

AN:

36104

South Asian (SAS)

AF:

0.00

AC:

AN:

79456

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48184

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.00000370

AC:

AN:

1080892

Other (OTH)

AF:

0.0000172

AC:

AN:

58022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

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

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

T;T;.

Eigen

Uncertain

0.38

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.95

D;D;D

M_CAP

Uncertain

0.089

MetaRNN

Uncertain

0.74

D;D;D

MetaSVM

Benign

-0.46

MutationAssessor

Pathogenic

3.0

M;.;.

PhyloP100

3.2

PrimateAI

Uncertain

0.63

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

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.48

gMVP

0.77

Mutation Taster

=80/20

polymorphism

(source)

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

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NM_007346.4:c.692C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over