12-11134216-G-A

Position:

• chr12-11134216-G-A

Variant summary

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

The NM_001097643.2(TAS2R30):​c.29C>T​(p.Ser10Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000543 in 1,611,958 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00061 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00054 (1 hom.)
• Consequence: TAS2R30 NM_001097643.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.312

Genes affected

TAS2R30 (HGNC:19112): (taste 2 receptor member 30) Enables bitter taste receptor activity. Involved in detection of chemical stimulus involved in sensory perception of bitter taste. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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]

PRH1-TAS2R14 (HGNC:):

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=0.026074737).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R30	NM_001097643.2	c.29C>T	p.Ser10Phe	missense_variant	1/1	ENST00000539585.1	NP_001091112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R30	ENST00000539585.1	c.29C>T	p.Ser10Phe	missense_variant	1/1	6	NM_001097643.2	ENSP00000444736.1

Frequencies

GnomAD3 genomes AF: 0.000612 AC: 93 AN: 152082 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000765

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000517 AC: 126 AN: 243762 Hom.: 0 AF XY: 0.000514 AC XY: 68 AN XY: 132372

Gnomad AFR exome AF: 0.000197

Gnomad AMR exome AF: 0.00138

Gnomad ASJ exome AF: 0.000409

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000673

Gnomad FIN exome AF: 0.0000937

Gnomad NFE exome AF: 0.000560

Gnomad OTH exome AF: 0.00119

GnomAD4 exome AF: 0.000536 AC: 783 AN: 1459876 Hom.: 1 Cov.: 38 AF XY: 0.000509 AC XY: 370 AN XY: 726208

Gnomad4 AFR exome AF: 0.0000602

Gnomad4 AMR exome AF: 0.00113

Gnomad4 ASJ exome AF: 0.000499

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000698

Gnomad4 FIN exome AF: 0.000112

Gnomad4 NFE exome AF: 0.000614

Gnomad4 OTH exome AF: 0.000398

GnomAD4 genome AF: 0.000612 AC: 93 AN: 152082 Hom.: 0 Cov.: 33 AF XY: 0.000673 AC XY: 50 AN XY: 74298

Gnomad4 AFR AF: 0.0000724

Gnomad4 AMR AF: 0.00236

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000765

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000506 Hom.: 0

ExAC AF: 0.000430 AC: 52

EpiCase AF: 0.000764

EpiControl AF: 0.000476

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

Jul 06, 2021

The c.29C>T (p.S10F) alteration is located in exon 1 (coding exon 1) of the TAS2R30 gene. This alteration results from a C to T substitution at nucleotide position 29, causing the serine (S) at amino acid position 10 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	0.21
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.014
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.013	D
Polyphen		0.32	B
Vest4		0.20
MVP		0.24
MPC		0.013
ClinPred		0.040	T
GERP RS		-0.10
Varity_R		0.16
gMVP		0.31

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: rs781094611; hg19: chr12-11286815;