1-6570923-A-T

Variant names:

• chr1-6570923-A-T
• NM_138697.4:c.206A>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_138697.4(TAS1R1):​c.206A>T​(p.Asn69Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000965 in 1,450,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. N69S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: TAS1R1 NM_138697.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.812

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS1R1	NM_138697.4	c.206A>T	p.Asn69Ile	missense_variant	Exon 2 of 6	ENST00000333172.11	NP_619642.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS1R1	ENST00000333172.11	c.206A>T	p.Asn69Ile	missense_variant	Exon 2 of 6	1	NM_138697.4	ENSP00000331867.6
TAS1R1	ENST00000351136.7	c.206A>T	p.Asn69Ile	missense_variant	Exon 2 of 5	2		ENSP00000312558.5
TAS1R1	ENST00000415267.1	c.-20A>T		upstream_gene_variant		1		ENSP00000408448.1
TAS1R1	ENST00000411823.5	c.-20A>T		upstream_gene_variant		2		ENSP00000414166.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000965 AC: 14 AN: 1450892 Hom.: 0 Cov.: 31 AF XY: 0.0000125 AC XY: 9 AN XY: 720898

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000127

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	19
DANN	Benign	0.85
DEOGEN2	Benign	0.27	T;.
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.81	T;T
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.81	D;D
MetaSVM	Uncertain	0.23	D
MutationAssessor	Benign	2.0	M;M
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-4.3	D;D
REVEL	Uncertain	0.54
Sift	Uncertain	0.0030	D;T
Sift4G	Uncertain	0.017	D;D
Polyphen		1.0	D;D
Vest4		0.66
MutPred		0.56		Gain of catalytic residue at N69 (P = 0.1052);Gain of catalytic residue at N69 (P = 0.1052);
MVP		0.80
MPC		0.74
ClinPred		0.98	D
GERP RS		4.0
Varity_R		0.46
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr1-6630983; COSMIC: COSV100063012; COSMIC: COSV100063012;