1-6574641-C-T

Variant names:

• chr1-6574641-C-T
• rs781181685
• NM_138697.4:c.509C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_138697.4(TAS1R1):​c.509C>T​(p.Ala170Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000117 in 1,601,362 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (2 hom.)
• Consequence: TAS1R1 NM_138697.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.970
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19080356).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138697.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS1R1	NM_138697.4	MANE Select	c.509C>T	p.Ala170Val	missense	Exon 3 of 6	NP_619642.2
	TAS1R1	NM_177540.3		c.499-1774C>T		intron	N/A	NP_803884.1	Q7RTX1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS1R1	ENST00000333172.11	TSL:1 MANE Select	c.509C>T	p.Ala170Val	missense	Exon 3 of 6	ENSP00000331867.6	Q7RTX1-1
	TAS1R1	ENST00000415267.1	TSL:1	c.274-1774C>T		intron	N/A	ENSP00000408448.1	H0Y6X0
	TAS1R1	ENST00000411823.5	TSL:2	c.284C>T	p.Ala95Val	missense	Exon 2 of 3	ENSP00000414166.1	H7C3W7

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152246 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000289 AC: 7 AN: 242422 AF XY: 0.0000383

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 FIN exome AF: 0.0000480

Gnomad NFE exome AF: 0.0000274

Gnomad OTH exome AF: 0.000338

GnomAD4 exome AF: 0.000124 AC: 179 AN: 1449116 Hom.: 2 Cov.: 30 AF XY: 0.000110 AC XY: 79 AN XY: 719308

African (AFR) AF: 0.0000300 AC: 1 AN: 33314

American (AMR) AF: 0.0000226 AC: 1 AN: 44202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39564

South Asian (SAS) AF: 0.0000356 AC: 3 AN: 84224

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52760

Middle Eastern (MID) AF: 0.000350 AC: 2 AN: 5710

European-Non Finnish (NFE) AF: 0.000151 AC: 167 AN: 1104370

Other (OTH) AF: 0.0000668 AC: 4 AN: 59870

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152246 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74374

African (AFR) AF: 0.0000723 AC: 3 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68044

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	12
DANN	Benign	0.81
DEOGEN2	Benign	0.17	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.97
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.44
Sift	Benign	0.046	D
Sift4G	Benign	0.20	T
Polyphen		0.18	B
Vest4		0.10
MVP		0.31
MPC		0.21
ClinPred		0.083	T
GERP RS		-9.1
Varity_R		0.093
gMVP		0.40
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs781181685; hg19: chr1-6634701; COSMIC: COSV60228055;