5-9629196-T-G

Position:

• chr5-9629196-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_019599.3(TAS2R1):​c.837A>C​(p.Leu279Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,441,424 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TAS2R1 NM_019599.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.407

Genes affected

TAS2R1 (HGNC:14909): (taste 2 receptor member 1) This gene encodes a member of a family of candidate taste receptors that are members of the G protein-coupled receptor superfamily and that are specifically expressed by taste receptor cells of the tongue and palate epithelia. This intronless taste receptor gene encodes a 7-transmembrane receptor protein, functioning as a bitter taste receptor. This gene is mapped to chromosome 5p15, the location of a genetic locus (PROP) that controls the detection of the bitter compound 6-n-propyl-2-thiouracil. [provided by RefSeq, Jul 2008]

ENSG00000248525 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29473713).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R1	NM_019599.3	c.837A>C	p.Leu279Phe	missense_variant	1/1	ENST00000382492.4	NP_062545.1
TAS2R1	NM_001386348.1	c.717A>C	p.Leu239Phe	missense_variant	10/10		NP_001373277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R1	ENST00000382492.4	c.837A>C	p.Leu279Phe	missense_variant	1/1	6	NM_019599.3	ENSP00000371932.2
ENSG00000248525	ENST00000504182.2	n.36-5594A>C		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1441424 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 716880

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.05e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 16, 2024

The c.837A>C (p.L279F) alteration is located in exon 1 (coding exon 1) of the TAS2R1 gene. This alteration results from a A to C substitution at nucleotide position 837, causing the leucine (L) at amino acid position 279 to be replaced by a phenylalanine (F). 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	0.096
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.061
MutPred		0.80		Loss of catalytic residue at L279 (P = 0.0502);
MVP		0.11
MPC		0.15
ClinPred		0.93	D
GERP RS		-6.6
Varity_R		0.46
gMVP		0.080

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs933530598; hg19: chr5-9629308;