12-11091786-G-T

Variant names:

• chr12-11091786-G-T
• rs775393495
• NM_176884.2:c.444C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_176884.2(TAS2R43):​c.444C>A​(p.Asn148Lys) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 24)
  • Failed GnomAD Quality Control
• Consequence: TAS2R43 NM_176884.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10
• Publications: 0 publications found

Genes affected

TAS2R43 (HGNC:18875): (taste 2 receptor member 43) TAS2R43 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]). For further information on TAS2Rs, see MIM 604791.[supplied by OMIM, Mar 2009]

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]

PRR4 (HGNC:18020): (proline rich 4) This gene encodes a member of the proline-rich protein family that lacks a conserved repetitive domain. This protein may play a role in protective functions in the eye. Alternative splicing result in multiple transcript variants. Read-through transcription also exists between this gene and the upstream PRH1 (proline-rich protein HaeIII subfamily 1) gene. [provided by RefSeq, Feb 2011]

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20197186).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_176884.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R43	NM_176884.2	MANE Select	c.444C>A	p.Asn148Lys	missense	Exon 1 of 1	NP_795365.2	P59537
	PRH1	NM_001291315.2		c.-133-44598C>A		intron	N/A	NP_001278244.1
	PRH1	NM_001291314.2		c.-294-44598C>A		intron	N/A	NP_001278243.1	A0A087WV42

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R43	ENST00000531678.1	TSL:6 MANE Select	c.444C>A	p.Asn148Lys	missense	Exon 1 of 1	ENSP00000431719.1	P59537
	ENSG00000275778	ENST00000536668.2	TSL:5	n.-164-44598C>A		intron	N/A	ENSP00000482961.1	A0A087WZY1
	PRR4	ENST00000535024.7	TSL:5	c.-133-44598C>A		intron	N/A	ENSP00000481571.3	A0A087WY73

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 131998 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD2 exomes AF: 0.00000474 AC: 1 AN: 211108 AF XY: 0.00000867

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000109

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 56

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 131998 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 64036

African (AFR) AF: 0.00 AC: 0 AN: 37398

American (AMR) AF: 0.00 AC: 0 AN: 13152

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3262

East Asian (EAS) AF: 0.00 AC: 0 AN: 5026

South Asian (SAS) AF: 0.00 AC: 0 AN: 4534

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 57506

Other (OTH) AF: 0.00 AC: 0 AN: 1800

ExAC AF: 0.00000832 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.32
DANN	Benign	0.63
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		-2.1
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.027
Sift	Benign	0.030	D
Sift4G	Benign	0.093	T
Polyphen		0.39	B
Vest4		0.20
MutPred		0.73		Gain of ubiquitination at N148 (P = 0.0238)
MVP		0.10
MPC		0.18
ClinPred		0.26	T
GERP RS		-1.9
Varity_R		0.13
gMVP		0.053
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs775393495; hg19: chr12-11244385;