NM_001004696.2:c.32C>A

Variant names:

• chr1-248361696-C-A
• rs774089576
• NM_001004696.2:c.32C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001004696.2(OR2T4):​c.32C>A​(p.Thr11Asn) 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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T11I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: OR2T4 NM_001004696.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 1 publications found

Genes affected

OR2T4 (HGNC:15016): (olfactory receptor family 2 subfamily T 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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15043283).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004696.2. 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
	OR2T4	NM_001004696.2	MANE Select	c.32C>A	p.Thr11Asn	missense	Exon 1 of 1	NP_001004696.2	A0A2C9F2M9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OR2T4	ENST00000366473.4	TSL:6 MANE Select	c.32C>A	p.Thr11Asn	missense	Exon 1 of 1	ENSP00000355429.3	A0A2C9F2M9

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.00000408 AC: 1 AN: 244948 AF XY: 0.00000754

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: 0.00000893

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ExAC AF: 0.00000837 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	12
DANN	Benign	0.81
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.3
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.033
Sift	Benign	0.082	T
Sift4G	Benign	0.11	T
Polyphen		0.18	B
Vest4		0.16
MutPred		0.48		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.54
MPC		0.16
ClinPred		0.10	T
GERP RS		1.6
PromoterAI		0.011	Neutral
Varity_R		0.084
gMVP		0.29
Mutation Taster		=91/9	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: rs774089576; hg19: chr1-248524998;