chr1-6575187-G-C

Position:

• chr1-6575187-G-C

Variant summary

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

The NM_138697.4(TAS1R1):​c.1055G>C​(p.Cys352Ser) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TAS1R1 NM_138697.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.85

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=0.13805065).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS1R1	NM_138697.4	c.1055G>C	p.Cys352Ser	missense_variant	3/6	ENST00000333172.11	NP_619642.2
LOC107984912	XR_002958250.1	n.87+4160C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS1R1	ENST00000333172.11	c.1055G>C	p.Cys352Ser	missense_variant	3/6	1	NM_138697.4	ENSP00000331867	P1
TAS1R1	ENST00000415267.1	c.276-1228G>C		intron_variant		1		ENSP00000408448
TAS1R1	ENST00000411823.5	c.833G>C	p.Cys278Ser	missense_variant	2/3	2		ENSP00000414166
TAS1R1	ENST00000351136.7	c.499-1228G>C		intron_variant		2		ENSP00000312558

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

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

Mar 19, 2024

The c.1055G>C (p.C352S) alteration is located in exon 3 (coding exon 3) of the TAS1R1 gene. This alteration results from a G to C substitution at nucleotide position 1055, causing the cysteine (C) at amino acid position 352 to be replaced by a serine (S). 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	Uncertain	0.44
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	16
DANN	Benign	0.41
DEOGEN2	Benign	0.056	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.56	T
MutationAssessor	Uncertain	2.0	M
MutationTaster	Benign	0.64	D;N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.27
Sift	Benign	0.88	T
Sift4G	Benign	0.78	T
Polyphen		0.16	B
Vest4		0.26
MutPred		0.46		Gain of phosphorylation at C352 (P = 0.0102);
MVP		0.57
MPC		0.26
ClinPred		0.20	T
GERP RS		5.1
Varity_R		0.25
gMVP		0.44

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: chr1-6635247;