NM_138697.4:c.859G>C

Variant names:

• chr1-6574991-G-C
• NM_138697.4:c.859G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138697.4(TAS1R1):​c.859G>C​(p.Val287Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000691 in 1,446,596 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V287M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TAS1R1 NM_138697.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.59

Genes affected

TAS1R1 (HGNC:14448): (taste 1 receptor member 1) The protein encoded by this gene is a G protein-coupled receptor and is a component of the heterodimeric amino acid taste receptor T1R1+3. The T1R1+3 receptor responds to L-amino acids but not to D-enantiomers or other compounds. Most amino acids that are perceived as sweet activate T1R1+3, and this activation is strictly dependent on an intact T1R1+3 heterodimer. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

LOC107984912 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS1R1	NM_138697.4	c.859G>C	p.Val287Leu	missense_variant	Exon 3 of 6	ENST00000333172.11	NP_619642.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS1R1	ENST00000333172.11	c.859G>C	p.Val287Leu	missense_variant	Exon 3 of 6	1	NM_138697.4	ENSP00000331867.6
TAS1R1	ENST00000415267.1	c.274-1424G>C		intron_variant	Intron 1 of 3	1		ENSP00000408448.1
TAS1R1	ENST00000411823.5	c.634G>C	p.Val212Leu	missense_variant	Exon 2 of 3	2		ENSP00000414166.1
TAS1R1	ENST00000351136.7	c.499-1424G>C		intron_variant	Intron 2 of 4	2		ENSP00000312558.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446596 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 717648

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Uncertain	0.16	D
MutationAssessor	Benign	1.6	L
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.57
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.42
MutPred		0.68		Loss of MoRF binding (P = 0.1241);
MVP		0.66
MPC		0.62
ClinPred		0.97	D
GERP RS		5.4
Varity_R		0.66
gMVP		0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-6635051;