1-6571100-A-G

Variant names:

• chr1-6571100-A-G
• NM_138697.4:c.383A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138697.4(TAS1R1):​c.383A>G​(p.Glu128Gly) variant causes a missense 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TAS1R1 NM_138697.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00500

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13327703).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS1R1	NM_138697.4	c.383A>G	p.Glu128Gly	missense_variant	Exon 2 of 6	ENST00000333172.11	NP_619642.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS1R1	ENST00000333172.11	c.383A>G	p.Glu128Gly	missense_variant	Exon 2 of 6	1	NM_138697.4	ENSP00000331867.6
TAS1R1	ENST00000415267.1	c.158A>G	p.Glu53Gly	missense_variant	Exon 1 of 4	1		ENSP00000408448.1
TAS1R1	ENST00000351136.7	c.383A>G	p.Glu128Gly	missense_variant	Exon 2 of 5	2		ENSP00000312558.5
TAS1R1	ENST00000411823.5	c.158A>G	p.Glu53Gly	missense_variant	Exon 1 of 3	2		ENSP00000414166.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.383A>G (p.E128G) alteration is located in exon 2 (coding exon 2) of the TAS1R1 gene. This alteration results from a A to G substitution at nucleotide position 383, causing the glutamic acid (E) at amino acid position 128 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	15
DANN	Benign	0.91
DEOGEN2	Benign	0.12	T;.
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;L
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.7	D;N
REVEL	Benign	0.13
Sift	Benign	0.17	T;D
Sift4G	Benign	0.34	T;D
Polyphen		0.0010	B;B
Vest4		0.29
MutPred		0.54		Loss of stability (P = 0.0582);Loss of stability (P = 0.0582);
MVP		0.59
MPC		0.20
ClinPred		0.30	T
GERP RS		1.2
Varity_R		0.17
gMVP		0.45

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-6631160;