chr12-11133489-A-C

Variant names:

• chr12-11133489-A-C
• rs2599404
• NM_001097643.2:c.756T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001097643.2(TAS2R30):​c.756T>G​(p.Phe252Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 1,611,678 control chromosomes in the GnomAD database, including 198,980 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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: 𝑓 0.45 (15603 hom., cov: 32)
  • Exomes 𝑓: 0.49 (183377 hom.)
• Consequence: TAS2R30 NM_001097643.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.718
• Publications: 29 publications found

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]

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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.312748E-5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001097643.2. 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
	TAS2R30	NM_001097643.2	MANE Select	c.756T>G	p.Phe252Leu	missense	Exon 1 of 1	NP_001091112.1
	PRH1	NM_001291315.2		c.-134+37933T>G		intron	N/A	NP_001278244.1
	PRH1	NM_001291314.2		c.-295+37933T>G		intron	N/A	NP_001278243.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R30	ENST00000539585.1	TSL:6 MANE Select	c.756T>G	p.Phe252Leu	missense	Exon 1 of 1	ENSP00000444736.1
	ENSG00000275778	ENST00000536668.2	TSL:5	n.-165+37933T>G		intron	N/A	ENSP00000482961.1
	PRR4	ENST00000535024.7	TSL:5	c.-134+37933T>G		intron	N/A	ENSP00000481571.3

Frequencies

GnomAD3 genomes AF: 0.449 AC: 67444 AN: 150368 Hom.: 15605 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.311

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.421

GnomAD2 exomes AF: 0.444 AC: 111285 AN: 250648 AF XY: 0.438

Gnomad AFR exome AF: 0.370

Gnomad AMR exome AF: 0.445

Gnomad ASJ exome AF: 0.350

Gnomad EAS exome AF: 0.212

Gnomad FIN exome AF: 0.597

Gnomad NFE exome AF: 0.515

Gnomad OTH exome AF: 0.453

GnomAD4 exome AF: 0.493 AC: 720671 AN: 1461196 Hom.: 183377 Cov.: 97 AF XY: 0.487 AC XY: 353707 AN XY: 726870

African (AFR) AF: 0.365 AC: 12218 AN: 33466

American (AMR) AF: 0.447 AC: 19985 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 9035 AN: 26132

East Asian (EAS) AF: 0.225 AC: 8923 AN: 39698

South Asian (SAS) AF: 0.278 AC: 23941 AN: 86220

European-Finnish (FIN) AF: 0.599 AC: 32010 AN: 53400

Middle Eastern (MID) AF: 0.323 AC: 1864 AN: 5766

European-Non Finnish (NFE) AF: 0.526 AC: 585000 AN: 1111452

Other (OTH) AF: 0.459 AC: 27695 AN: 60370

GnomAD4 genome AF: 0.448 AC: 67456 AN: 150482 Hom.: 15603 Cov.: 32 AF XY: 0.447 AC XY: 32886 AN XY: 73540

African (AFR) AF: 0.358 AC: 14758 AN: 41186

American (AMR) AF: 0.444 AC: 6708 AN: 15110

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1159 AN: 3442

East Asian (EAS) AF: 0.216 AC: 1115 AN: 5152

South Asian (SAS) AF: 0.265 AC: 1266 AN: 4782

European-Finnish (FIN) AF: 0.586 AC: 6079 AN: 10370

Middle Eastern (MID) AF: 0.314 AC: 91 AN: 290

European-Non Finnish (NFE) AF: 0.518 AC: 34819 AN: 67164

Other (OTH) AF: 0.417 AC: 868 AN: 2080

Alfa AF: 0.487 Hom.: 12889

Bravo AF: 0.438

TwinsUK AF: 0.534 AC: 1980

ALSPAC AF: 0.536 AC: 2064

ESP6500AA AF: 0.377 AC: 1662

ESP6500EA AF: 0.504 AC: 4332

ExAC AF: 0.439 AC: 53243

Asia WGS AF: 0.300 AC: 1045 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.084
DANN	Benign	0.21
DEOGEN2	Benign	0.0095	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.000033	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.76	N
PhyloP100		-0.72
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.019
Sift	Benign	0.67	T
Sift4G	Benign	0.65	T
Vest4		0.044
MutPred		0.41		Loss of methylation at K257 (P = 0.0941)
MPC		0.0047
ClinPred		0.0084	T
GERP RS		-3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.027
gMVP		0.030
Mutation Taster		=100/0	polymorphism (auto)

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: rs2599404; hg19: chr12-11286088; COSMIC: COSV67856082;