chr12-10939193-T-C

Position:

• chr12-10939193-T-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_023922.2(TAS2R14):​c.15A>G​(p.Ile5Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000582 in 1,573,182 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0032 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00030 (2 hom.)
• Consequence: TAS2R14 NM_023922.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.974

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]

PRH1-TAS2R14 (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 Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0037686527).
• BP6: Variant 12-10939193-T-C is Benign according to our data. Variant chr12-10939193-T-C is described in ClinVar as [Benign]. Clinvar id is 717257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R14	NM_023922.2	c.15A>G	p.Ile5Met	missense_variant	1/1	ENST00000537503.2	NP_076411.1
PRH1-TAS2R14	NM_001316893.2	c.208-616A>G		intron_variant			NP_001303822.1
PRH1-PRR4	NR_037918.2	n.544+34462A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R14	ENST00000537503.2	c.15A>G	p.Ile5Met	missense_variant	1/1		NM_023922.2	ENSP00000441949	P1
	ENST00000703543.1	c.-59+34462A>G		intron_variant				ENSP00000515364	P1

Frequencies

GnomAD3 genomes AF: 0.00319 AC: 485 AN: 152228 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.000978 AC: 204 AN: 208516 Hom.: 0 AF XY: 0.000678 AC XY: 76 AN XY: 112012

Gnomad AFR exome AF: 0.0136

Gnomad AMR exome AF: 0.0000664

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000196

GnomAD4 exome AF: 0.000301 AC: 427 AN: 1420836 Hom.: 2 Cov.: 30 AF XY: 0.000260 AC XY: 183 AN XY: 704132

Gnomad4 AFR exome AF: 0.0113

Gnomad4 AMR exome AF: 0.000172

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000457

Gnomad4 OTH exome AF: 0.000763

GnomAD4 genome AF: 0.00321 AC: 489 AN: 152346 Hom.: 3 Cov.: 32 AF XY: 0.00336 AC XY: 250 AN XY: 74504

Gnomad4 AFR AF: 0.0114

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000507 Hom.: 1

Bravo AF: 0.00319

ESP6500AA AF: 0.00902 AC: 39

ESP6500EA AF: 0.000119 AC: 1

ExAC AF: 0.00112 AC: 135

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 24, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.4
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0036	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.010	N
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.80	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.78	N
REVEL	Benign	0.070
Sift	Benign	0.090	T
Sift4G	Uncertain	0.041	D
Polyphen		0.44	B
Vest4		0.10
MVP		0.10
MPC		0.023
ClinPred		0.030	T
GERP RS		-0.67
Varity_R		0.091
gMVP		0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs79297986; hg19: chr12-11091792;