1-1334174-T-C

Position:

• chr1-1334174-T-C

Variant summary

Our verdict is Benign. Variant got -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. 15/19 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS1R3	NM_152228.3	c.2269T>C	p.Cys757Arg	missense_variant	6/6	ENST00000339381.6	NP_689414.2
TAS1R3	XM_017002435.2	c.2395T>C	p.Cys799Arg	missense_variant	5/5		XP_016857924.1
TAS1R3	XM_017002436.2	c.2392T>C	p.Cys798Arg	missense_variant	5/5		XP_016857925.1
TAS1R3	XM_047431571.1	c.2266T>C	p.Cys756Arg	missense_variant	6/6		XP_047287527.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS1R3	ENST00000339381.6	c.2269T>C	p.Cys757Arg	missense_variant	6/6	2	NM_152228.3	ENSP00000344411	P1

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

GnomAD3 exomes AF: 0.961 AC: 206771 AN: 215220 Hom.: 99421 AF XY: 0.958 AC XY: 112256 AN XY: 117122

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 SAS exome AF: 0.922

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

Gnomad4 AFR exome AF: 0.988

Gnomad4 AMR exome AF: 0.986

Gnomad4 ASJ exome AF: 0.982

Gnomad4 EAS exome AF: 0.892

Gnomad4 SAS exome AF: 0.921

Gnomad4 FIN exome AF: 0.930

Gnomad4 NFE exome AF: 0.973

Gnomad4 OTH exome AF: 0.963

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

Gnomad4 AFR AF: 0.988

Gnomad4 AMR AF: 0.980

Gnomad4 ASJ AF: 0.977

Gnomad4 EAS AF: 0.908

Gnomad4 SAS AF: 0.914

Gnomad4 FIN AF: 0.923

Gnomad4 NFE AF: 0.973

Gnomad4 OTH AF: 0.966

Alfa AF: 0.972 Hom.: 71494

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 v4.3

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
MutationTaster	Benign	1.0	P
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

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

LitVar

Other links and lift over

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