11-56136825-A-T

Position:

• chr11-56136825-A-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001004064.2(OR8J3):​c.894T>A​(p.Asn298Lys) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OR8J3 NM_001004064.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.21

Genes affected

OR8J3 (HGNC:15312): (olfactory receptor family 8 subfamily J member 3) Predicted to enable odorant binding activity and olfactory receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway and sensory perception of smell. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03848043).
• BP6: Variant 11-56136825-A-T is Benign according to our data. Variant chr11-56136825-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 3206801.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OR8J3	NM_001004064.2	c.894T>A	p.Asn298Lys	missense_variant	2/2	ENST00000642058.1	NP_001004064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OR8J3	ENST00000642058.1	c.894T>A	p.Asn298Lys	missense_variant	2/2		NM_001004064.2	ENSP00000493166	P1
OR8J3	ENST00000641913.1	c.894T>A	p.Asn298Lys	missense_variant	2/2			ENSP00000493417	P1
OR8J3	ENST00000641489.1	n.243T>A		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 19, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.015
DANN	Benign	0.13
DEOGEN2	Benign	0.0020	T;T;T
Eigen	Benign	-2.7
Eigen_PC	Benign	-2.6
FATHMM_MKL	Benign	0.0010	N
LIST_S2	Benign	0.15	.;.;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.038	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.7	N;N;N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	4.3	.;.;N
REVEL	Benign	0.078
Sift	Benign	1.0	.;.;T
Sift4G	Benign	1.0	.;.;T
Polyphen		0.0	B;B;B
Vest4		0.11
MutPred		0.51		Gain of methylation at N298 (P = 0.0124);Gain of methylation at N298 (P = 0.0124);Gain of methylation at N298 (P = 0.0124);
MVP		0.11
MPC		0.0091
ClinPred		0.067	T
GERP RS		-4.4
Varity_R		0.029
gMVP		0.27

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: chr11-55904301;