chr1-6575199-C-T

Variant names:

• chr1-6575199-C-T
• rs41307749
• NM_138697.4:c.1067C>T

Variant summary

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

The NM_138697.4(TAS1R1):​c.1067C>T​(p.Ser356Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,112 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TAS1R1 NM_138697.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS1R1	NM_138697.4	MANE Select	c.1067C>T	p.Ser356Phe	missense	Exon 3 of 6	NP_619642.2
	TAS1R1	NM_177540.3		c.499-1216C>T		intron	N/A	NP_803884.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS1R1	ENST00000333172.11	TSL:1 MANE Select	c.1067C>T	p.Ser356Phe	missense	Exon 3 of 6	ENSP00000331867.6
	TAS1R1	ENST00000415267.1	TSL:1	c.274-1216C>T		intron	N/A	ENSP00000408448.1
	TAS1R1	ENST00000411823.5	TSL:2	c.842C>T	p.Ser281Phe	missense	Exon 2 of 3	ENSP00000414166.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459112 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 725858

African (AFR) AF: 0.0000299 AC: 1 AN: 33390

American (AMR) AF: 0.00 AC: 0 AN: 44360

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25892

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 85958

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110774

Other (OTH) AF: 0.00 AC: 0 AN: 60262

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.070	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.39	T
MutationAssessor	Benign	0.48	N
PhyloP100		1.3
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.35
Sift	Uncertain	0.023	D
Sift4G	Uncertain	0.021	D
Polyphen		1.0	D
Vest4		0.38
MutPred		0.60		Loss of disorder (P = 0.0106)
MVP		0.63
MPC		0.68
ClinPred		0.35	T
GERP RS		4.5
Varity_R		0.21
gMVP		0.35
Mutation Taster		=93/7	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: rs41307749; hg19: chr1-6635259;