12-10938960-C-T

Variant names:

• chr12-10938960-C-T
• NM_023922.2:c.248G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_023922.2(TAS2R14):​c.248G>A​(p.Arg83Lys) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAS2R14 NM_023922.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.90
• Publications: 0 publications found

Genes affected

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]

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057741463).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023922.2. 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
	TAS2R14	NM_023922.2	MANE Select	c.248G>A	p.Arg83Lys	missense	Exon 1 of 1	NP_076411.1	Q9NYV8
	PRH1	NM_001291315.2		c.103+34695G>A		intron	N/A	NP_001278244.1
	PRH1	NM_001291314.2		c.-59+34695G>A		intron	N/A	NP_001278243.1	A0A087WV42

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R14	ENST00000537503.2	TSL:6 MANE Select	c.248G>A	p.Arg83Lys	missense	Exon 1 of 1	ENSP00000441949.1	Q9NYV8
	ENSG00000275778	ENST00000536668.2	TSL:5	n.176+34695G>A		intron	N/A	ENSP00000482961.1	A0A087WZY1
	PRH1	ENST00000703543.1		c.-59+34695G>A		intron	N/A	ENSP00000515364.1	A0A087WYT0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.046
DANN	Benign	0.62
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0027	N
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.3	L
PhyloP100		-2.9
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.072
Sift	Benign	0.46	T
Sift4G	Benign	0.53	T
Polyphen		0.030	B
Vest4		0.031
MutPred		0.53		Gain of methylation at R83 (P = 0.0308)
MVP		0.18
MPC		0.018
ClinPred		0.066	T
GERP RS		-5.8
PromoterAI		-0.011	Neutral
Varity_R		0.086
gMVP		0.16
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

hg19: chr12-11091559;