12-11030656-G-C

Position:

• chr12-11030656-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_176885.2(TAS2R31):​c.680C>G​(p.Ala227Gly) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A227V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TAS2R31 NM_176885.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.492

Genes affected

TAS2R31 (HGNC:19113): (taste 2 receptor member 31) TAS2R44 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.797

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R31	NM_176885.2	c.680C>G	p.Ala227Gly	missense_variant	1/1	ENST00000390675.2	NP_795366.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R31	ENST00000390675.2	c.680C>G	p.Ala227Gly	missense_variant	1/1	6	NM_176885.2	ENSP00000375093.2
ENSG00000275778	ENST00000703543.1	c.-126+16364C>G		intron_variant				ENSP00000515364.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 127

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	21
DANN	Benign	0.93
DEOGEN2	Benign	0.093	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.039	N
M_CAP	Benign	0.0013	T
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.9	M
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.11
Sift	Benign	0.049	D
Sift4G	Benign	0.11	T
Polyphen		1.0	D
Vest4		0.37
MutPred		0.86		Loss of ubiquitination at K226 (P = 0.093);
MVP		0.15
MPC		0.094
ClinPred		0.59	D
GERP RS		1.4
Varity_R		0.20
gMVP		0.068

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.48		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.48		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10845293; hg19: chr12-11183255;