1-1334174-T-C

Variant names:

• chr1-1334174-T-C
• rs307377
• NM_152228.3:c.2269T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152228.3(TAS1R3):​c.2269T>C​(p.Cys757Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.967 in 1,594,094 control chromosomes in the GnomAD database, including 745,711 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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: 𝑓 0.97 (71774 hom., cov: 35)
  • Exomes 𝑓: 0.97 (673937 hom.)
• Consequence: TAS1R3 NM_152228.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.360
• Publications: 38 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.3400132E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.98 is higher than 0.05.

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.2269T>C	p.Cys757Arg	missense	Exon 6 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.2269T>C	p.Cys757Arg	missense	Exon 6 of 6	ENSP00000344411.5	Q7RTX0

Frequencies

GnomAD3 genomes AF: 0.970 AC: 147724 AN: 152236 Hom.: 71719 Cov.: 35

Gnomad AFR AF: 0.988

Gnomad AMI AF: 0.959

Gnomad AMR AF: 0.980

Gnomad ASJ AF: 0.977

Gnomad EAS AF: 0.908

Gnomad SAS AF: 0.915

Gnomad FIN AF: 0.923

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.974

Gnomad OTH AF: 0.967

GnomAD2 exomes AF: 0.961 AC: 206771 AN: 215220 AF XY: 0.958

Gnomad AFR exome AF: 0.988

Gnomad AMR exome AF: 0.988

Gnomad ASJ exome AF: 0.983

Gnomad EAS exome AF: 0.914

Gnomad FIN exome AF: 0.926

Gnomad NFE exome AF: 0.973

Gnomad OTH exome AF: 0.955

GnomAD4 exome AF: 0.967 AC: 1393644 AN: 1441740 Hom.: 673937 Cov.: 104 AF XY: 0.965 AC XY: 690797 AN XY: 715638

African (AFR) AF: 0.988 AC: 32777 AN: 33176

American (AMR) AF: 0.986 AC: 41075 AN: 41664

Ashkenazi Jewish (ASJ) AF: 0.982 AC: 25249 AN: 25720

East Asian (EAS) AF: 0.892 AC: 34483 AN: 38656

South Asian (SAS) AF: 0.921 AC: 77293 AN: 83894

European-Finnish (FIN) AF: 0.930 AC: 47113 AN: 50682

Middle Eastern (MID) AF: 0.939 AC: 5400 AN: 5748

European-Non Finnish (NFE) AF: 0.973 AC: 1072843 AN: 1102582

Other (OTH) AF: 0.963 AC: 57411 AN: 59618

GnomAD4 genome AF: 0.970 AC: 147839 AN: 152354 Hom.: 71774 Cov.: 35 AF XY: 0.967 AC XY: 72063 AN XY: 74502

African (AFR) AF: 0.988 AC: 41092 AN: 41584

American (AMR) AF: 0.980 AC: 15003 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.977 AC: 3392 AN: 3472

East Asian (EAS) AF: 0.908 AC: 4707 AN: 5184

South Asian (SAS) AF: 0.914 AC: 4418 AN: 4832

European-Finnish (FIN) AF: 0.923 AC: 9803 AN: 10618

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.973 AC: 66228 AN: 68032

Other (OTH) AF: 0.966 AC: 2043 AN: 2114

Alfa AF: 0.971 Hom.: 190405

Bravo AF: 0.976

TwinsUK AF: 0.974 AC: 3613

ALSPAC AF: 0.972 AC: 3746

ESP6500AA AF: 0.990 AC: 4332

ESP6500EA AF: 0.971 AC: 8325

ExAC AF: 0.957 AC: 114238

Asia WGS AF: 0.900 AC: 3130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	1.0
DANN	Benign	0.51
DEOGEN2	Benign	0.088	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.22	T
MetaRNN	Benign	0.0000023	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-2.1	N
PhyloP100		0.36
PrimateAI	Benign	0.29	T
PROVEAN	Benign	4.1	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.028
ClinPred		0.0035	T
GERP RS		-0.84
Varity_R		0.23
gMVP		0.39
Mutation Taster		=99/1	polymorphism (auto)

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: rs307377; hg19: chr1-1269554; COSMIC: COSV59564749; COSMIC: COSV59564749;