1-6575072-G-T

Variant names:

• chr1-6575072-G-T
• rs767970228
• NM_138697.4:c.940G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_138697.4(TAS1R1):​c.940G>T​(p.Gly314Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000000696 in 1,436,354 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. G314R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: TAS1R1 NM_138697.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.29
• 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.884

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.940G>T	p.Gly314Trp	missense	Exon 3 of 6	NP_619642.2
	TAS1R1	NM_177540.3		c.499-1343G>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.940G>T	p.Gly314Trp	missense	Exon 3 of 6	ENSP00000331867.6	Q7RTX1-1
	TAS1R1	ENST00000415267.1	TSL:1	c.274-1343G>T		intron	N/A	ENSP00000408448.1	H0Y6X0
	TAS1R1	ENST00000411823.5	TSL:2	c.715G>T	p.Gly239Trp	missense	Exon 2 of 3	ENSP00000414166.1	H7C3W7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436354 Hom.: 0 Cov.: 30 AF XY: 0.00000140 AC XY: 1 AN XY: 711754

African (AFR) AF: 0.00 AC: 0 AN: 32850

American (AMR) AF: 0.00 AC: 0 AN: 42412

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24140

East Asian (EAS) AF: 0.00 AC: 0 AN: 39488

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 81902

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5616

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1098470

Other (OTH) AF: 0.00 AC: 0 AN: 59188

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.42	T
Eigen	Uncertain	0.37
Eigen_PC	Benign	0.20
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Uncertain	0.24	D
MutationAssessor	Pathogenic	3.0	M
PhyloP100		5.3
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.55
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.63
MutPred		0.67		Gain of MoRF binding (P = 0.0202)
MVP		0.84
MPC		0.75
ClinPred		0.99	D
GERP RS		3.5
Varity_R		0.88
gMVP		0.80
Mutation Taster		=70/30	polymorphism

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

Other links and lift over

dbSNP: rs767970228; hg19: chr1-6635132;