1-1331814-G-T

Variant names:

• chr1-1331814-G-T
• rs759426688
• NM_152228.3:c.368G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152228.3(TAS1R3):​c.368G>T​(p.Arg123Leu) 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 1,460,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R123H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TAS1R3 NM_152228.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234
• Publications: 0 publications found

Genes affected

TAS1R3 (HGNC:15661): (taste 1 receptor member 3) The protein encoded by this gene is a G-protein coupled receptor involved in taste responses. The encoded protein can form a heterodimeric receptor with TAS1R1 to elicit the umami taste response, or it can bind with TAS1R2 to form a receptor for the sweet taste response. [provided by RefSeq, Nov 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08100417).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152228.3. 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
	TAS1R3	NM_152228.3	MANE Select	c.368G>T	p.Arg123Leu	missense	Exon 2 of 6	NP_689414.2	Q7RTX0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS1R3	ENST00000339381.6	TSL:2 MANE Select	c.368G>T	p.Arg123Leu	missense	Exon 2 of 6	ENSP00000344411.5	Q7RTX0

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460512 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726540

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52074

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	0.60
DANN	Benign	0.67
DEOGEN2	Benign	0.10	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.73	T
M_CAP	Uncertain	0.085	D
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.23
PrimateAI	Benign	0.19	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.19
Sift	Benign	0.30	T
Sift4G	Benign	0.38	T
Polyphen		0.32	B
Vest4		0.14
MutPred		0.35		Loss of solvent accessibility (P = 0.0052)
MVP		0.31
ClinPred		0.74	D
GERP RS		1.5
Varity_R		0.12
gMVP		0.49
Mutation Taster		=95/5	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: rs759426688; hg19: chr1-1267194;