NM_138697.4:c.1027C>G

Variant names:

• chr1-6575159-C-G
• rs534607431
• NM_138697.4:c.1027C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138697.4(TAS1R1):​c.1027C>G​(p.Arg343Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,441,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign 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. R343W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: TAS1R1 NM_138697.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.04
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18853998).

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.1027C>G	p.Arg343Gly	missense	Exon 3 of 6	NP_619642.2
	TAS1R1	NM_177540.3		c.499-1256C>G		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.1027C>G	p.Arg343Gly	missense	Exon 3 of 6	ENSP00000331867.6	Q7RTX1-1
	TAS1R1	ENST00000415267.1	TSL:1	c.274-1256C>G		intron	N/A	ENSP00000408448.1	H0Y6X0
	TAS1R1	ENST00000411823.5	TSL:2	c.802C>G	p.Arg268Gly	missense	Exon 2 of 3	ENSP00000414166.1	H7C3W7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000436 AC: 1 AN: 229462 AF XY: 0.00000806

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: 0.00

Gnomad NFE exome AF: 0.00000955

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000167 AC: 24 AN: 1441418 Hom.: 0 Cov.: 30 AF XY: 0.0000181 AC XY: 13 AN XY: 716298

African (AFR) AF: 0.00 AC: 0 AN: 32564

American (AMR) AF: 0.00 AC: 0 AN: 41080

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24324

East Asian (EAS) AF: 0.00 AC: 0 AN: 39620

South Asian (SAS) AF: 0.0000120 AC: 1 AN: 83008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5634

European-Non Finnish (NFE) AF: 0.0000199 AC: 22 AN: 1103346

Other (OTH) AF: 0.0000168 AC: 1 AN: 59410

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	0.0040
DANN	Benign	0.73
DEOGEN2	Benign	0.29	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.46	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	2.0	M
PhyloP100		-3.0
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.33
Sift	Benign	0.036	D
Sift4G	Benign	0.19	T
Polyphen		0.24	B
Vest4		0.22
MutPred		0.54		Loss of MoRF binding (P = 0.0147)
MVP		0.54
MPC		0.29
ClinPred		0.27	T
GERP RS		-3.1
Varity_R		0.20
gMVP		0.25
Mutation Taster		=95/5	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: rs534607431; hg19: chr1-6635219;