chr3-98264649-C-T

Variant names:

• chr3-98264649-C-T
• rs372483864
• NM_001005479.2:c.317C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001005479.2(OR5H6):​c.317C>T​(p.Thr106Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000028 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR5H6 NM_001005479.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.09
• Publications: 1 publications found

Genes affected

OR5H6 (HGNC:14767): (olfactory receptor family 5 subfamily H member 6) 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. This olfactory receptor gene is a segregating pseudogene, where some individuals have an allele that encodes a functional olfactory receptor, while other individuals have an allele encoding a protein that is predicted to be non-functional. [provided by RefSeq, Jul 2015]

ENSG00000251088 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.067273885).
• BP6: Variant 3-98264649-C-T is Benign according to our data. Variant chr3-98264649-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2305559.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005479.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR5H6	NM_001005479.2	MANE Select	c.317C>T	p.Thr106Ile	missense	Exon 1 of 1	NP_001005479.2	A0A126GW86

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR5H6	ENST00000615035.3	TSL:6 MANE Select	c.317C>T	p.Thr106Ile	missense	Exon 1 of 1	ENSP00000480705.3	A0A126GW86
	ENSG00000251088	ENST00000508616.1	TSL:1	n.26+30973C>T		intron	N/A
	OR5H6	ENST00000642105.1		c.365C>T	p.Thr122Ile	missense	Exon 1 of 1	ENSP00000493340.1	Q8NGV6

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 53484 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 248668 AF XY: 0.00

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000283 AC: 1 AN: 353220 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 177572

African (AFR) AF: 0.00 AC: 0 AN: 19496

American (AMR) AF: 0.00 AC: 0 AN: 22668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7122

East Asian (EAS) AF: 0.00 AC: 0 AN: 33226

South Asian (SAS) AF: 0.00 AC: 0 AN: 32206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1522

European-Non Finnish (NFE) AF: 0.00000480 AC: 1 AN: 208400

Other (OTH) AF: 0.00 AC: 0 AN: 16220

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 53484 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 26362

African (AFR) AF: 0.00 AC: 0 AN: 23480

American (AMR) AF: 0.00 AC: 0 AN: 5870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 924

East Asian (EAS) AF: 0.00 AC: 0 AN: 4098

South Asian (SAS) AF: 0.00 AC: 0 AN: 1808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 98

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 13768

Other (OTH) AF: 0.00 AC: 0 AN: 666

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000377 AC: 3

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.40
DANN	Benign	0.39
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0026	N
LIST_S2	Benign	0.0093	T
M_CAP	Benign	0.00030	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.60	N
PhyloP100		-2.1
PrimateAI	Benign	0.22	T
Polyphen		0.0	B
ClinPred		0.055	T
GERP RS		0.71
PromoterAI		0.0012	Neutral
Varity_R		0.030
gMVP		0.059
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs372483864; hg19: chr3-97983493;