11-56105352-T-A

Variant names:

• chr11-56105352-T-A
• NM_001386064.1:c.310T>A

Variant summary

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

The NM_001386064.1(OR8H2):​c.310T>A​(p.Phe104Ile) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: OR8H2 NM_001386064.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.636

Genes affected

OR8H2 (HGNC:15308): (olfactory receptor family 8 subfamily H member 2) 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=0.1590999).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR8H2	NM_001386064.1	c.310T>A	p.Phe104Ile	missense_variant	Exon 2 of 2	ENST00000313503.2	NP_001372993.1
OR8H2	NM_001005200.2	c.310T>A	p.Phe104Ile	missense_variant	Exon 2 of 2		NP_001005200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR8H2	ENST00000313503.2	c.310T>A	p.Phe104Ile	missense_variant	Exon 2 of 2	6	NM_001386064.1	ENSP00000323982.1
OR8H2	ENST00000641311.1	c.310T>A	p.Phe104Ile	missense_variant	Exon 2 of 2			ENSP00000493031.1
OR8H2	ENST00000618136.1	c.307T>A	p.Phe103Ile	missense_variant	Exon 1 of 1	6		ENSP00000482661.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.310T>A (p.F104I) alteration is located in exon 1 (coding exon 1) of the OR8H2 gene. This alteration results from a T to A substitution at nucleotide position 310, causing the phenylalanine (F) at amino acid position 104 to be replaced by an isoleucine (I). 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	0.17
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0098	T;T;.
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.71	.;T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;L;.
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-4.7	D;.;.
REVEL	Benign	0.072
Sift	Uncertain	0.0060	D;.;.
Sift4G	Uncertain	0.0070	D;.;D
Polyphen		0.98	D;D;.
Vest4		0.31
MutPred		0.36		Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);.;
MVP		0.23
MPC		0.56
ClinPred		0.98	D
GERP RS		3.6
Varity_R		0.52
gMVP		0.22

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-55872828;