NM_023920.2:c.578T>G

Variant names:

• chr12-10908721-A-C
• rs375488942
• NM_023920.2:c.578T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_023920.2(TAS2R13):​c.578T>G​(p.Val193Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TAS2R13 NM_023920.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.48
• Publications: 0 publications found

Genes affected

TAS2R13 (HGNC:14919): (taste 2 receptor member 13) 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26759267).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023920.2. 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
	TAS2R13	NM_023920.2	MANE Select	c.578T>G	p.Val193Gly	missense	Exon 1 of 1	NP_076409.1	Q9NYV9
	PRH1	NM_001291315.2		c.104-25625T>G		intron	N/A	NP_001278244.1
	PRH1	NM_001291314.2		c.-58-24446T>G		intron	N/A	NP_001278243.1	A0A087WV42

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R13	ENST00000390677.2	TSL:6 MANE Select	c.578T>G	p.Val193Gly	missense	Exon 1 of 1	ENSP00000375095.2	Q9NYV9
	ENSG00000275778	ENST00000536668.2	TSL:5	n.177-24446T>G		intron	N/A	ENSP00000482961.1	A0A087WZY1
	PRH1	ENST00000703543.1		c.-58-24446T>G		intron	N/A	ENSP00000515364.1	A0A087WYT0

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 32

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461572 Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3 AN XY: 727068

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111856

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74362

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2094

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00 AC: 0

ClinVar

ClinVar submissions

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	0.21
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.046	N
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		1.5
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.089
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.93	P
Vest4		0.23
MVP		0.42
MPC		0.045
ClinPred		0.61	D
GERP RS		0.64
Varity_R		0.89
gMVP		0.16
Mutation Taster		=96/4	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: rs375488942; hg19: chr12-11061320;