1-6575171-A-C

Variant names:

• chr1-6575171-A-C
• rs10864628
• NM_138697.4:c.1039A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_138697.4(TAS1R1):​c.1039A>C​(p.Lys347Gln) 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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 36)
• Consequence: TAS1R1 NM_138697.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130
• Publications: 26 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05426669).

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.1039A>C	p.Lys347Gln	missense	Exon 3 of 6	NP_619642.2
	TAS1R1	NM_177540.3		c.499-1244A>C		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.1039A>C	p.Lys347Gln	missense	Exon 3 of 6	ENSP00000331867.6	Q7RTX1-1
	TAS1R1	ENST00000415267.1	TSL:1	c.274-1244A>C		intron	N/A	ENSP00000408448.1	H0Y6X0
	TAS1R1	ENST00000411823.5	TSL:2	c.814A>C	p.Lys272Gln	missense	Exon 2 of 3	ENSP00000414166.1	H7C3W7

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome Cov.: 88

GnomAD4 genome Cov.: 36

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	3.5
DANN	Benign	0.36
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.24	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.59	N
PhyloP100		-0.13
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.16
Sift	Benign	0.59	T
Sift4G	Benign	0.58	T
Polyphen		0.0010	B
Vest4		0.10
MutPred		0.28		Loss of methylation at K347 (P = 0.0155)
MVP		0.82
MPC		0.18
ClinPred		0.033	T
GERP RS		-0.46
Varity_R		0.074
gMVP		0.26
Mutation Taster		=99/1	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: rs10864628; hg19: chr1-6635231;