12-10826263-G-A

Position:

• chr12-10826263-G-A

Variant summary

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

The NM_023921.2(TAS2R10):​c.7C>T​(p.Arg3Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000701 in 1,597,780 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000066 (0 hom.)
• Consequence: TAS2R10 NM_023921.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0140

Genes affected

TAS2R10 (HGNC:14918): (taste 2 receptor member 10) 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]

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.030591726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R10	NM_023921.2	c.7C>T	p.Arg3Cys	missense_variant	1/1	ENST00000240619.3	NP_076410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R10	ENST00000240619.3	c.7C>T	p.Arg3Cys	missense_variant	1/1	6	NM_023921.2	ENSP00000240619.2
PRH1	ENST00000538332.2	c.*19-1070C>T		intron_variant		5		ENSP00000481761.1

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 151984 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000263

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000113 AC: 27 AN: 238634 Hom.: 0 AF XY: 0.0000926 AC XY: 12 AN XY: 129530

Gnomad AFR exome AF: 0.000127

Gnomad AMR exome AF: 0.000640

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad SAS exome AF: 0.0000695

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000922

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000657 AC: 95 AN: 1445678 Hom.: 0 Cov.: 29 AF XY: 0.0000529 AC XY: 38 AN XY: 718828

Gnomad4 AFR exome AF: 0.000580

Gnomad4 AMR exome AF: 0.000445

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000177

Gnomad4 SAS exome AF: 0.0000236

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000408

Gnomad4 OTH exome AF: 0.0000502

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152102 Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74350

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.000128

ExAC AF: 0.000115 AC: 14

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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

Apr 06, 2023

The c.7C>T (p.R3C) alteration is located in exon 1 (coding exon 1) of the TAS2R10 gene. This alteration results from a C to T substitution at nucleotide position 7, causing the arginine (R) at amino acid position 3 to be replaced by a cysteine (C). 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	0.21
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	15
DANN	Benign	0.88
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.014	N
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.056
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.013	D
Polyphen		0.48	P
Vest4		0.085
MVP		0.34
MPC		0.0084
ClinPred		0.024	T
GERP RS		-1.3
Varity_R		0.16
gMVP		0.24

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: rs201235220; hg19: chr12-10978862;