1-6555384-G-C

Variant names:

• chr1-6555384-G-C
• rs35375392
• NM_138697.4:c.11G>C

Variant summary

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

The NM_138697.4(TAS1R1):​c.11G>C​(p.Cys4Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,486 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TAS1R1 NM_138697.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 0 publications found

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]

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=0.08995345).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138697.4. 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
	TAS1R1	NM_138697.4	MANE Select	c.11G>C	p.Cys4Ser	missense	Exon 1 of 6	NP_619642.2
	TAS1R1	NM_177540.3		c.11G>C	p.Cys4Ser	missense	Exon 1 of 5	NP_803884.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS1R1	ENST00000333172.11	TSL:1 MANE Select	c.11G>C	p.Cys4Ser	missense	Exon 1 of 6	ENSP00000331867.6
	TAS1R1	ENST00000351136.7	TSL:2	c.11G>C	p.Cys4Ser	missense	Exon 1 of 5	ENSP00000312558.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447486 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 719212

African (AFR) AF: 0.00 AC: 0 AN: 33294

American (AMR) AF: 0.00 AC: 0 AN: 43652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25876

East Asian (EAS) AF: 0.00 AC: 0 AN: 39198

South Asian (SAS) AF: 0.00 AC: 0 AN: 84562

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5614

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1106866

Other (OTH) AF: 0.00 AC: 0 AN: 59826

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	0.042
DANN	Benign	0.44
DEOGEN2	Benign	0.046	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.065	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-0.62	T
PhyloP100		-1.3
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.54	N
REVEL	Benign	0.18
Sift	Benign	0.40	T
Sift4G	Benign	0.41	T
Polyphen		0.0010	B
Vest4		0.14
MutPred		0.60		Gain of disorder (P = 0)
MVP		0.27
MPC		0.20
ClinPred		0.53	D
GERP RS		-4.9
PromoterAI		-0.027	Neutral
Varity_R		0.11
gMVP		0.58
Mutation Taster		=100/0	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: rs35375392; hg19: chr1-6615444;