11-124310048-G-C

Variant names:

• chr11-124310048-G-C
• NM_001002917.2:c.719C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001002917.2(OR8D1):​c.719C>G​(p.Thr240Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR8D1 NM_001002917.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.11

Genes affected

OR8D1 (HGNC:8481): (olfactory receptor family 8 subfamily D member 1) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.856

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR8D1	NM_001002917.2	c.719C>G	p.Thr240Arg	missense_variant	Exon 3 of 3	ENST00000641015.1	NP_001002917.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR8D1	ENST00000641015.1	c.719C>G	p.Thr240Arg	missense_variant	Exon 3 of 3		NM_001002917.2	ENSP00000493365.1
OR8D1	ENST00000357821.2	c.719C>G	p.Thr240Arg	missense_variant	Exon 1 of 1	6		ENSP00000350474.2
OR8D1	ENST00000641897.1	c.719C>G	p.Thr240Arg	missense_variant	Exon 4 of 4			ENSP00000493091.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.719C>G (p.T240R) alteration is located in exon 1 (coding exon 1) of the OR8D1 gene. This alteration results from a C to G substitution at nucleotide position 719, causing the threonine (T) at amino acid position 240 to be replaced by an arginine (R). 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	Uncertain	0.52
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.014	T;T;T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	.;.;D
M_CAP	Benign	0.0049	T
MetaRNN	Pathogenic	0.86	D;D;D
MetaSVM	Uncertain	0.30	D
MutationAssessor	Pathogenic	4.1	H;H;H
PrimateAI	Benign	0.20	T
PROVEAN	Pathogenic	-5.8	.;.;D
REVEL	Uncertain	0.42
Sift	Pathogenic	0.0	.;.;D
Sift4G	Pathogenic	0.0	.;.;D
Polyphen		1.0	D;D;D
Vest4		0.64
MutPred		0.63		Loss of ubiquitination at K236 (P = 0.0184);Loss of ubiquitination at K236 (P = 0.0184);Loss of ubiquitination at K236 (P = 0.0184);
MVP		0.57
MPC		0.17
ClinPred		0.99	D
GERP RS		4.3
Varity_R		0.90
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-124179944;