11-123907369-C-T

Variant names:

• chr11-123907369-C-T
• rs147695757
• NM_001005197.2:c.938C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001005197.2(OR8D4):​c.938C>T​(p.Pro313Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000191 in 1,045,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: OR8D4 NM_001005197.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.214

Genes affected

OR8D4 (HGNC:14840): (olfactory receptor family 8 subfamily D member 4) 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0710952).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR8D4	NM_001005197.2	c.938C>T	p.Pro313Leu	missense_variant	Exon 2 of 2	ENST00000641687.1	NP_001005197.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR8D4	ENST00000641687.1	c.938C>T	p.Pro313Leu	missense_variant	Exon 2 of 2		NM_001005197.2	ENSP00000493391.1
OR8D4	ENST00000321355.3	c.938C>T	p.Pro313Leu	missense_variant	Exon 1 of 1	6		ENSP00000325381.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000102 AC: 2 AN: 196706 Hom.: 0 AF XY: 0.00000947 AC XY: 1 AN XY: 105616

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.0000214

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000191 AC: 2 AN: 1045438 Hom.: 0 Cov.: 14 AF XY: 0.00000189 AC XY: 1 AN XY: 529256

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000262

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.8
DANN	Benign	0.76
DEOGEN2	Benign	0.0078	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0091	N
LIST_S2	Benign	0.36	.;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.071	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.12	.;N
REVEL	Benign	0.011
Sift	Benign	0.12	.;T
Sift4G	Uncertain	0.010	.;D
Polyphen		0.0	B;B
Vest4		0.13
MutPred		0.37		Loss of glycosylation at P313 (P = 0.0242);Loss of glycosylation at P313 (P = 0.0242);
MVP		0.12
MPC		0.015
ClinPred		0.044	T
GERP RS		0.31
Varity_R		0.021
gMVP		0.099

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

Other links and lift over

dbSNP: rs147695757; hg19: chr11-123778076;