12-10938599-G-A

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_023922.2(TAS2R14):​c.609C>T​(p.Phe203=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00353 in 1,613,948 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0037 ( 14 hom. )

Consequence

TAS2R14
NM_023922.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.10
Variant links:
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 (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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant 12-10938599-G-A is Benign according to our data. Variant chr12-10938599-G-A is described in ClinVar as [Benign]. Clinvar id is 791051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.11 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TAS2R14NM_023922.2 linkuse as main transcriptc.609C>T p.Phe203= synonymous_variant 1/1 ENST00000537503.2 NP_076411.1
PRH1-TAS2R14NM_001316893.2 linkuse as main transcriptc.208-22C>T intron_variant NP_001303822.1
PRH1-PRR4NR_037918.2 linkuse as main transcriptn.544+35056C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TAS2R14ENST00000537503.2 linkuse as main transcriptc.609C>T p.Phe203= synonymous_variant 1/1 NM_023922.2 ENSP00000441949 P1
ENST00000703543.1 linkuse as main transcriptc.-59+35056C>T intron_variant ENSP00000515364 P1

Frequencies

GnomAD3 genomes
AF:
0.00225
AC:
342
AN:
152164
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000820
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00124
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00113
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00401
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.00232
AC:
581
AN:
250850
Hom.:
3
AF XY:
0.00252
AC XY:
341
AN XY:
135564
show subpopulations
Gnomad AFR exome
AF:
0.000923
Gnomad AMR exome
AF:
0.00136
Gnomad ASJ exome
AF:
0.0000994
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00158
Gnomad NFE exome
AF:
0.00417
Gnomad OTH exome
AF:
0.00164
GnomAD4 exome
AF:
0.00367
AC:
5359
AN:
1461666
Hom.:
14
Cov.:
31
AF XY:
0.00349
AC XY:
2541
AN XY:
727120
show subpopulations
Gnomad4 AFR exome
AF:
0.000538
Gnomad4 AMR exome
AF:
0.00137
Gnomad4 ASJ exome
AF:
0.0000766
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.00176
Gnomad4 NFE exome
AF:
0.00451
Gnomad4 OTH exome
AF:
0.00267
GnomAD4 genome
AF:
0.00225
AC:
342
AN:
152282
Hom.:
2
Cov.:
32
AF XY:
0.00211
AC XY:
157
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.000818
Gnomad4 AMR
AF:
0.00124
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00113
Gnomad4 NFE
AF:
0.00401
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.00313
Hom.:
0
Bravo
AF:
0.00249
EpiCase
AF:
0.00365
EpiControl
AF:
0.00415

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 12, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.83
DANN
Benign
0.75

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs117092928; hg19: chr12-11091198; API