7-143222770-C-A

Variant names:

• chr7-143222770-C-A
• rs747633325
• NM_176882.2:c.692C>A

Variant summary

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

The NM_176882.2(TAS2R40):​c.692C>A​(p.Ala231Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TAS2R40 NM_176882.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.391

Genes affected

TAS2R40 (HGNC:18885): (taste 2 receptor member 40) This gene encodes a member of the bitter taste receptor family which belong to the G protein-coupled receptor superfamily and are predominantly expressed in taste receptor cells of the tongue and palate epithelia. This intronless taste receptor gene encodes a seven-transmembrane receptor protein, functioning as a bitter taste receptor. This gene is clustered together with eight other taste receptor genes on chromosome 7. A decrease in the expression of this gene is associated with hypogeusia. [provided by RefSeq, Jul 2017]

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, 0.79

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS2R40	NM_176882.2	c.692C>A	p.Ala231Asp	missense_variant	Exon 1 of 1	ENST00000408947.4	NP_795363.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS2R40	ENST00000408947.4	c.692C>A	p.Ala231Asp	missense_variant	Exon 1 of 1	6	NM_176882.2	ENSP00000386210.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461864 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727230

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 28, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.692C>A (p.A231D) alteration is located in exon 1 (coding exon 1) of the TAS2R40 gene. This alteration results from a C to A substitution at nucleotide position 692, causing the alanine (A) at amino acid position 231 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0093	T
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.14
Sift	Benign	0.060	T
Sift4G	Benign	0.098	T
Polyphen		0.92	P
Vest4		0.46
MutPred		0.71		Loss of glycosylation at S234 (P = 0.1027);
MVP		0.74
MPC		0.29
ClinPred		0.99	D
GERP RS		3.8
Varity_R		0.51
gMVP		0.21

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

Publications

LitVar

Other links and lift over

dbSNP: rs747633325; hg19: chr7-142919863;