14-18601137-G-T

Variant names:

• chr14-18601137-G-T
• rs200891589
• NM_001013354.1:c.21G>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001013354.1(OR11H12):​c.21G>T​(p.Gln7His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00072 (0 hom., cov: 20)
  • Exomes 𝑓: 0.00027 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: OR11H12 NM_001013354.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.264

Genes affected

OR11H12 (HGNC:30738): (olfactory receptor family 11 subfamily H member 12) 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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.035033703).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OR11H12	NM_001013354.1	c.21G>T	p.Gln7His	missense_variant	Exon 1 of 1	ENST00000550708.2	NP_001013372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OR11H12	ENST00000550708.2	c.21G>T	p.Gln7His	missense_variant	Exon 1 of 1	6	NM_001013354.1	ENSP00000449002.1

Frequencies

GnomAD3 genomes AF: 0.000719 AC: 100 AN: 139080 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000501

Gnomad ASJ AF: 0.000311

Gnomad EAS AF: 0.000211

Gnomad SAS AF: 0.00117

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00370

Gnomad NFE AF: 0.000444

Gnomad OTH AF: 0.000534

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000270 AC: 375 AN: 1389094 Hom.: 2 Cov.: 25 AF XY: 0.000277 AC XY: 192 AN XY: 694278

Gnomad4 AFR exome AF: 0.00141

Gnomad4 AMR exome AF: 0.000544

Gnomad4 ASJ exome AF: 0.000200

Gnomad4 EAS exome AF: 0.000203

Gnomad4 SAS exome AF: 0.000306

Gnomad4 FIN exome AF: 0.0000380

Gnomad4 NFE exome AF: 0.000228

Gnomad4 OTH exome AF: 0.000384

GnomAD4 genome AF: 0.000718 AC: 100 AN: 139194 Hom.: 0 Cov.: 20 AF XY: 0.000692 AC XY: 47 AN XY: 67954

Gnomad4 AFR AF: 0.00151

Gnomad4 AMR AF: 0.000500

Gnomad4 ASJ AF: 0.000311

Gnomad4 EAS AF: 0.000211

Gnomad4 SAS AF: 0.00117

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000444

Gnomad4 OTH AF: 0.000527

Alfa AF: 0.000397 Hom.: 0

ExAC AF: 0.000148 AC: 16

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 22, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.21G>T (p.Q7H) alteration is located in exon 1 (coding exon 1) of the OR11H12 gene. This alteration results from a G to T substitution at nucleotide position 21, causing the glutamine (Q) at amino acid position 7 to be replaced by a histidine (H). 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	0.11
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	2.4
DANN	Benign	0.48
DEOGEN2	Benign	0.0010	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0095	N
LIST_S2	Benign	0.26	T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.3	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.024
Sift	Benign	0.17	T
Sift4G	Benign	0.10	T
Polyphen		0.69	P
Vest4		0.12
MutPred		0.35		Gain of catalytic residue at V8 (P = 0);
MVP		0.40
MPC		2.3
ClinPred		0.011	T
Varity_R		0.11
gMVP		0.095

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

Publications

LitVar

Other links and lift over

dbSNP: rs200891589; hg19: chr14-19377614;