chr1-6574973-A-G

Position:

• chr1-6574973-A-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.841A>G​(p.Arg281Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAS1R1 NM_138697.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.45

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=0.1432178).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS1R1	NM_138697.4	c.841A>G	p.Arg281Gly	missense_variant	3/6	ENST00000333172.11	NP_619642.2
LOC107984912	XR_002958250.1	n.87+4374T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS1R1	ENST00000333172.11	c.841A>G	p.Arg281Gly	missense_variant	3/6	1	NM_138697.4	ENSP00000331867	P1
TAS1R1	ENST00000415267.1	c.276-1442A>G		intron_variant		1		ENSP00000408448
TAS1R1	ENST00000411823.5	c.619A>G	p.Arg207Gly	missense_variant	2/3	2		ENSP00000414166
TAS1R1	ENST00000351136.7	c.499-1442A>G		intron_variant		2		ENSP00000312558

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2022

The c.841A>G (p.R281G) alteration is located in exon 3 (coding exon 3) of the TAS1R1 gene. This alteration results from a A to G substitution at nucleotide position 841, causing the arginine (R) at amino acid position 281 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	0.13
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	9.1
DANN	Benign	0.95
DEOGEN2	Benign	0.16	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.2	N
REVEL	Uncertain	0.36
Sift	Benign	0.31	T
Sift4G	Benign	0.28	T
Polyphen		0.015	B
Vest4		0.15
MutPred		0.65		Gain of catalytic residue at V282 (P = 0.0169);
MVP		0.79
MPC		0.23
ClinPred		0.096	T
GERP RS		-6.7
Varity_R		0.21
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr1-6635033;