1-1331509-C-A

Variant names:

• chr1-1331509-C-A
• rs372183680
• NM_152228.3:c.164C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_152228.3(TAS1R3):​c.164C>A​(p.Thr55Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000237 in 1,600,930 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: TAS1R3 NM_152228.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0740
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.107937574).

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.164C>A	p.Thr55Lys	missense	Exon 1 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.164C>A	p.Thr55Lys	missense	Exon 1 of 6	ENSP00000344411.5	Q7RTX0

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152242 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000675

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000323 AC: 7 AN: 216762 AF XY: 0.0000251

Gnomad AFR exome AF: 0.000570

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000690 AC: 10 AN: 1448688 Hom.: 0 Cov.: 31 AF XY: 0.00000417 AC XY: 3 AN XY: 719946

African (AFR) AF: 0.000272 AC: 9 AN: 33136

American (AMR) AF: 0.00 AC: 0 AN: 42386

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25858

East Asian (EAS) AF: 0.00 AC: 0 AN: 39078

South Asian (SAS) AF: 0.00 AC: 0 AN: 85012

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106374

Other (OTH) AF: 0.0000167 AC: 1 AN: 59820

GnomAD4 genome AF: 0.000184 AC: 28 AN: 152242 Hom.: 0 Cov.: 34 AF XY: 0.000215 AC XY: 16 AN XY: 74382

African (AFR) AF: 0.000675 AC: 28 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000717 Hom.: 0

Bravo AF: 0.000162

ESP6500AA AF: 0.000465 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000333 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.12
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.077	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.074
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.29
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.032	D
Polyphen		0.97	D
Vest4		0.43
MVP		0.57
ClinPred		0.20	T
GERP RS		2.2
PromoterAI		0.16	Neutral
Varity_R		0.15
gMVP		0.50
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs372183680; hg19: chr1-1266889;