1-6575171-A-T

Variant names:

• chr1-6575171-A-T
• rs10864628
• NM_138697.4:c.1039A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_138697.4(TAS1R1):​c.1039A>T​(p.Lys347*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 36)
• Consequence: TAS1R1 NM_138697.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130
• Publications: 26 publications found

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

Our verdict: Uncertain_significance. The variant received 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.1039A>T	p.Lys347*	stop_gained	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.1039A>T	p.Lys347*	stop_gained	Exon 3 of 6	1	NM_138697.4	ENSP00000331867.6
TAS1R1	ENST00000415267.1	c.274-1244A>T		intron_variant	Intron 1 of 3	1		ENSP00000408448.1
TAS1R1	ENST00000411823.5	c.814A>T	p.Lys272*	stop_gained	Exon 2 of 3	2		ENSP00000414166.1
TAS1R1	ENST00000351136.7	c.499-1244A>T		intron_variant	Intron 2 of 4	2		ENSP00000312558.5

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome Cov.: 88

GnomAD4 genome Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	34
DANN	Uncertain	0.98
Eigen	Benign	-0.015
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.12	N
PhyloP100		-0.13
Vest4		0.41
ClinPred		0.72	D
GERP RS		-0.46
Mutation Taster		=38/162	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs10864628; hg19: chr1-6635231;