12-10986214-G-C

Position:

• chr12-10986214-G-C

Variant summary

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

The NM_176890.2(TAS2R50):​c.647C>G​(p.Ser216Trp) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAS2R50 NM_176890.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.785

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]

ENSG00000275778 (HGNC:):

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]

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=0.35297513).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R50	NM_176890.2	c.647C>G	p.Ser216Trp	missense_variant	1/1	ENST00000506868.1	NP_795371.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R50	ENST00000506868.1	c.647C>G	p.Ser216Trp	missense_variant	1/1	6	NM_176890.2	ENSP00000424040.1
ENSG00000275778	ENST00000703543.1	c.-125-12493C>G		intron_variant				ENSP00000515364.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 66

GnomAD4 genome Cov.: 32

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

Sep 20, 2024

The c.647C>G (p.S216W) alteration is located in exon 1 (coding exon 1) of the TAS2R50 gene. This alteration results from a C to G substitution at nucleotide position 647, causing the serine (S) at amino acid position 216 to be replaced by a tryptophan (W). 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	0.15
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.065	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.018	N
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Pathogenic	3.6	H
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.064
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.16	T
Polyphen		1.0	D
Vest4		0.26
MutPred		0.54		Loss of disorder (P = 8e-04);
MVP		0.53
MPC		0.067
ClinPred		0.94	D
GERP RS		-1.8
Varity_R		0.23
gMVP		0.082

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: chr12-11138813;