19-9214120-T-G

Variant summary

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

The NM_001005191.3(OR7D4):c.718A>C(p.Thr240Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000041 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: OR7D4 NM_001005191.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.54

Genes affected

OR7D4 (HGNC:8380): (olfactory receptor family 7 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]

OR7E24 (HGNC:):

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, 0.872

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OR7D4	NM_001005191.3	c.718A>C	p.Thr240Pro	missense_variant	2/2	ENST00000641669.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OR7D4	ENST00000641669.1	c.718A>C	p.Thr240Pro	missense_variant	2/2		NM_001005191.3	P1
OR7D4	ENST00000308682.3	c.718A>C	p.Thr240Pro	missense_variant	1/1			P1
OR7D4	ENST00000641244.1	c.718A>C	p.Thr240Pro	missense_variant	2/2			P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251444 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135904

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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461864 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727236

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: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2021

The c.718A>C (p.T240P) alteration is located in exon 1 (coding exon 1) of the OR7D4 gene. This alteration results from a A to C substitution at nucleotide position 718, causing the threonine (T) at amino acid position 240 to be replaced by a proline (P). 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	0.18
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.018	T;T;T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.79	D
M_CAP	Benign	0.0022	T
MetaRNN	Pathogenic	0.87	D;D;D
MetaSVM	Uncertain	0.030	D
MutationAssessor	Pathogenic	4.3	H;H;H
MutationTaster	Benign	0.99	D
PrimateAI	Benign	0.20	T
Polyphen		1.0	D;D;D
Vest4		0.41
MutPred		0.72		Gain of catalytic residue at T240 (P = 0.0937);Gain of catalytic residue at T240 (P = 0.0937);Gain of catalytic residue at T240 (P = 0.0937);
MVP		0.76
MPC		0.33
ClinPred		1.0	D
GERP RS		3.8
Varity_R		0.92
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs779947288; hg19: chr19-9324796;