rs1462496413

Variant names:

• chr1-6574911-T-C
• rs1462496413
• NM_138697.4:c.779T>C

Variant summary

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

The NM_138697.4(TAS1R1):​c.779T>C​(p.Met260Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000226 in 1,461,746 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: TAS1R1 NM_138697.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.83

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.779T>C	p.Met260Thr	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.779T>C	p.Met260Thr	missense_variant	Exon 3 of 6	1	NM_138697.4	ENSP00000331867.6
TAS1R1	ENST00000415267.1	c.274-1504T>C		intron_variant	Intron 1 of 3	1		ENSP00000408448.1
TAS1R1	ENST00000411823.5	c.554T>C	p.Met185Thr	missense_variant	Exon 2 of 3	2		ENSP00000414166.1
TAS1R1	ENST00000351136.7	c.499-1504T>C		intron_variant	Intron 2 of 4	2		ENSP00000312558.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000797 AC: 2 AN: 250844 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 135588

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000226 AC: 33 AN: 1461746 Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21 AN XY: 727158

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.0000297

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 10, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.779T>C (p.M260T) alteration is located in exon 3 (coding exon 3) of the TAS1R1 gene. This alteration results from a T to C substitution at nucleotide position 779, causing the methionine (M) at amino acid position 260 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	16
DANN	Benign	0.93
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.053
Eigen_PC	Benign	-0.086
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.067	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Uncertain	0.063	D
MutationAssessor	Benign	1.5	L
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.49
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.67	P
Vest4		0.24
MutPred		0.71		Loss of stability (P = 0.0435);
MVP		0.76
MPC		0.20
ClinPred		0.40	T
GERP RS		4.9
Varity_R		0.46
gMVP		0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs1462496413; hg19: chr1-6634971;