12-10986070-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_176890.2(TAS2R50):​c.791G>A​(p.Ser264Asn) 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

TAS2R50
NM_176890.2 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.17
Variant links:
Genes affected
TAS2R50 (HGNC:18882): (taste 2 receptor member 50) TAS2R50 belongs to the large TAS2R receptor family. TAS2Rs are expressed on the surface of taste receptor cells and mediate the perception of bitterness through a G protein-coupled second messenger pathway (Conte et al., 2002 [PubMed 12584440]). See also TAS2R10 (MIM 604791).[supplied by OMIM, Mar 2008]
PRH1 (HGNC:9366): (proline rich protein HaeIII subfamily 1) This gene encodes a member of the heterogeneous family of proline-rich salivary glycoproteins. The encoded preproprotein undergoes proteolytic processing to generate one or more mature isoforms before secretion from the parotid and submandibular/sublingual glands. Multiple distinct alleles of this locus including the parotid isoelectric-focusing variant slow (PIF-s), the parotid acidic protein (Pa), and the double band slow (Db-s) isoforms have been characterized. The reference genome encodes the Db-s allele. Certain alleles of this gene are associated with susceptibility to dental caries. This gene is located in a cluster of closely related salivary proline-rich proteins on chromosome 12. Co-transcription of this gene with adjacent genes has been observed. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2015]
TAS2R14 (HGNC:14920): (taste 2 receptor member 14) This gene product belongs to the family of candidate taste receptors that are members of the G-protein-coupled receptor superfamily. These proteins are specifically expressed in the taste receptor cells of the tongue and palate epithelia. They are organized in the genome in clusters and are genetically linked to loci that influence bitter perception in mice and humans. In functional expression studies, they respond to bitter tastants. This gene maps to the taste receptor gene cluster on chromosome 12p13. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13390413).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TAS2R50NM_176890.2 linkc.791G>A p.Ser264Asn missense_variant Exon 1 of 1 ENST00000506868.1 NP_795371.2 P59544

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TAS2R50ENST00000506868.1 linkc.791G>A p.Ser264Asn missense_variant Exon 1 of 1 6 NM_176890.2 ENSP00000424040.1 P59544
ENSG00000275778ENST00000703543.1 linkc.-125-12349G>A intron_variant Intron 1 of 3 ENSP00000515364.1 A0A087WYT0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 09, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.791G>A (p.S264N) alteration is located in exon 1 (coding exon 1) of the TAS2R50 gene. This alteration results from a G to A substitution at nucleotide position 791, causing the serine (S) at amino acid position 264 to be replaced by an asparagine (N). 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
0.19
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
6.6
DANN
Benign
0.92
DEOGEN2
Benign
0.0023
T
Eigen
Benign
-0.97
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.014
N
M_CAP
Benign
0.0029
T
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
1.3
L
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-1.7
N
REVEL
Benign
0.026
Sift
Uncertain
0.0030
D
Sift4G
Benign
0.073
T
Polyphen
0.17
B
Vest4
0.11
MutPred
0.57
Loss of catalytic residue at K265 (P = 0.043);
MVP
0.23
MPC
0.027
ClinPred
0.12
T
GERP RS
-0.45
Varity_R
0.25
gMVP
0.15

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: chr12-11138669; API