chr1-6574750-C-A

Position:

• chr1-6574750-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_138697.4(TAS1R1):​c.618C>A​(p.Phe206Leu) 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 pathogenic 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: -1.29

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.841

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS1R1	NM_138697.4	c.618C>A	p.Phe206Leu	missense_variant	3/6	ENST00000333172.11	NP_619642.2
LOC107984912	XR_002958250.1	n.87+4597G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS1R1	ENST00000333172.11	c.618C>A	p.Phe206Leu	missense_variant	3/6	1	NM_138697.4	ENSP00000331867	P1
TAS1R1	ENST00000415267.1	c.276-1665C>A		intron_variant		1		ENSP00000408448
TAS1R1	ENST00000411823.5	c.396C>A	p.Phe132Leu	missense_variant	2/3	2		ENSP00000414166
TAS1R1	ENST00000351136.7	c.499-1665C>A		intron_variant		2		ENSP00000312558

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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 21, 2023

The c.618C>A (p.F206L) alteration is located in exon 3 (coding exon 3) of the TAS1R1 gene. This alteration results from a C to A substitution at nucleotide position 618, causing the phenylalanine (F) at amino acid position 206 to be replaced by a leucine (L). 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	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	8.8
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.10	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	0.99	D;D;D
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Uncertain	0.55
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.039	D
Polyphen		1.0	D
Vest4		0.37
MutPred		0.85		Loss of methylation at K205 (P = 0.0282);
MVP		0.67
MPC		0.68
ClinPred		0.99	D
GERP RS		-3.4
Varity_R		0.77
gMVP		0.59

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: chr1-6634810;