12-10939019-G-A

Variant names:

• chr12-10939019-G-A
• rs142263768
• NM_023922.2:c.189C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_023922.2(TAS2R14):​c.189C>T​(p.Phe63Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00699 in 1,613,458 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0072 (50 hom.)
• Consequence: TAS2R14 NM_023922.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -7.62
• Publications: 5 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: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 12-10939019-G-A is Benign according to our data. Variant chr12-10939019-G-A is described in ClinVar as Benign. ClinVar VariationId is 719366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-7.62 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.189C>T	p.Phe63Phe	synonymous	Exon 1 of 1	NP_076411.1	Q9NYV8
	PRH1	NM_001291315.2		c.103+34636C>T		intron	N/A	NP_001278244.1
	PRH1	NM_001291314.2		c.-59+34636C>T		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.189C>T	p.Phe63Phe	synonymous	Exon 1 of 1	ENSP00000441949.1	Q9NYV8
	ENSG00000275778	ENST00000536668.2	TSL:5	n.176+34636C>T		intron	N/A	ENSP00000482961.1	A0A087WZY1
	PRH1	ENST00000703543.1		c.-59+34636C>T		intron	N/A	ENSP00000515364.1	A0A087WYT0

Frequencies

GnomAD3 genomes AF: 0.00458 AC: 697 AN: 152152 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00113

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00320

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00829

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00497 AC: 1242 AN: 249968 AF XY: 0.00481

Gnomad AFR exome AF: 0.000493

Gnomad AMR exome AF: 0.000905

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00330

Gnomad NFE exome AF: 0.00942

Gnomad OTH exome AF: 0.00411

GnomAD4 exome AF: 0.00724 AC: 10581 AN: 1461188 Hom.: 50 Cov.: 36 AF XY: 0.00700 AC XY: 5089 AN XY: 726826

African (AFR) AF: 0.000628 AC: 21 AN: 33446

American (AMR) AF: 0.00114 AC: 51 AN: 44578

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00139 AC: 120 AN: 86108

European-Finnish (FIN) AF: 0.00384 AC: 205 AN: 53352

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 0.00887 AC: 9864 AN: 1111810

Other (OTH) AF: 0.00524 AC: 316 AN: 60354

GnomAD4 genome AF: 0.00458 AC: 698 AN: 152270 Hom.: 3 Cov.: 32 AF XY: 0.00393 AC XY: 293 AN XY: 74476

African (AFR) AF: 0.00113 AC: 47 AN: 41550

American (AMR) AF: 0.00183 AC: 28 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00320 AC: 34 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00831 AC: 565 AN: 68008

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00669 Hom.: 2

Bravo AF: 0.00417

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00813

EpiControl AF: 0.00701

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.3
DANN	Benign	0.69
PhyloP100		-7.6
PromoterAI		0.024	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs142263768; hg19: chr12-11091618;