chr7-141790741-T-G

Variant names:

• chr7-141790741-T-G
• rs906225124
• NM_018980.3:c.380T>G

Variant summary

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

The NM_018980.3(TAS2R5):​c.380T>G​(p.Leu127Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TAS2R5 NM_018980.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0600
• Publications: 0 publications found

Genes affected

TAS2R5 (HGNC:14912): (taste 2 receptor member 5) This gene encodes a bitter taste receptor; bitter taste receptors are members of the G protein-coupled receptor superfamily and are specifically expressed by taste receptor cells of the tongue and palate epithelia. Each of these apparently intronless taste receptor genes encodes a 7-transmembrane receptor protein, functioning as a bitter taste receptor. This gene is clustered with another 3 candidate taste receptor genes on chromosome 7 and is genetically linked to loci that influence bitter perception. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018980.3. 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
	TAS2R5	NM_018980.3	MANE Select	c.380T>G	p.Leu127Arg	missense	Exon 1 of 1	NP_061853.1	Q9NYW4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAS2R5	ENST00000247883.5	TSL:6 MANE Select	c.380T>G	p.Leu127Arg	missense	Exon 1 of 1	ENSP00000247883.4	Q9NYW4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461894 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727248

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

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	0.13
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	4.5
DANN	Benign	0.73
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.89
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0076	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.060
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.25
Sift	Benign	0.48	T
Sift4G	Benign	0.063	T
Polyphen		0.12	B
Vest4		0.30
MutPred		0.87		Gain of catalytic residue at L127 (P = 0.008)
MVP		0.16
MPC		0.14
ClinPred		0.21	T
GERP RS		-1.4
Varity_R		0.39
gMVP		0.12
Mutation Taster		=97/3	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: rs906225124; hg19: chr7-141490541;