1-6555473-C-G

Variant names:

• chr1-6555473-C-G
• rs867755137
• NM_138697.4:c.100C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138697.4(TAS1R1):​c.100C>G​(p.Leu34Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. L34F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TAS1R1 NM_138697.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31439394).

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.100C>G	p.Leu34Val	missense	Exon 1 of 6	NP_619642.2
	TAS1R1	NM_177540.3		c.100C>G	p.Leu34Val	missense	Exon 1 of 5	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.100C>G	p.Leu34Val	missense	Exon 1 of 6	ENSP00000331867.6	Q7RTX1-1
	TAS1R1	ENST00000351136.7	TSL:2	c.100C>G	p.Leu34Val	missense	Exon 1 of 5	ENSP00000312558.5	Q7RTX1-2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444938 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 717294

African (AFR) AF: 0.00 AC: 0 AN: 33066

American (AMR) AF: 0.00 AC: 0 AN: 42390

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25762

East Asian (EAS) AF: 0.00 AC: 0 AN: 38776

South Asian (SAS) AF: 0.00 AC: 0 AN: 83526

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52066

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1103846

Other (OTH) AF: 0.00 AC: 0 AN: 59760

GnomAD4 genome Cov.: 34

Alfa AF: 0.0000385 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.31	T
MetaSVM	Uncertain	0.42	D
PhyloP100		2.1
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.41
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.97	D
Vest4		0.19
MutPred		0.47		Gain of glycosylation at T33 (P = 0.0865)
MVP		0.43
MPC		0.65
ClinPred		0.95	D
GERP RS		3.3
PromoterAI		0.021	Neutral
Varity_R		0.29
gMVP		0.40
Mutation Taster		=83/17	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: rs867755137; hg19: chr1-6615533;