7-141764950-G-A

Position:

• chr7-141764950-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016943.2(TAS2R3):​c.792G>A​(p.Met264Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000062 (0 hom.)
• Consequence: TAS2R3 NM_016943.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.520

Genes affected

TAS2R3 (HGNC:14910): (taste 2 receptor member 3) This gene encodes a member of a family of candidate taste receptors that are members of the G protein-coupled receptor superfamily and that are specifically expressed by taste receptor cells of the tongue and palate epithelia. These apparently intronless taste receptor genes encode a 7-transmembrane receptor protein, functioning as a bitter taste receptor. This gene is clustered with another 3 candidate taste receptor genes in chromosome 7 and is genetically linked to loci that influence bitter perception. [provided by RefSeq, Jul 2008]

SSBP1 (HGNC:11317): (single stranded DNA binding protein 1) SSBP1 is a housekeeping gene involved in mitochondrial biogenesis (Tiranti et al., 1995 [PubMed 7789991]). It is also a subunit of a single-stranded DNA (ssDNA)-binding complex involved in the maintenance of genome stability (Huang et al., 2009) [PubMed 19683501].[supplied by OMIM, Feb 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.076565206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R3	NM_016943.2	c.792G>A	p.Met264Ile	missense_variant	1/1	ENST00000247879.2	NP_058639.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R3	ENST00000247879.2	c.792G>A	p.Met264Ile	missense_variant	1/1	6	NM_016943.2	ENSP00000247879.2
SSBP1	ENST00000465582.5	c.*30+14566G>A		intron_variant		5		ENSP00000420485.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461884 Hom.: 0 Cov.: 70 AF XY: 0.00000688 AC XY: 5 AN XY: 727242

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: 0.00000629

Gnomad4 OTH exome AF: 0.0000331

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000611 Hom.: 0

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 25, 2024

The c.792G>A (p.M264I) alteration is located in exon 1 (coding exon 1) of the TAS2R3 gene. This alteration results from a G to A substitution at nucleotide position 792, causing the methionine (M) at amino acid position 264 to be replaced by an isoleucine (I). 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	0.15
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.58
DANN	Benign	0.58
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.097	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.38	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.023
Sift	Benign	0.10	T
Sift4G	Benign	0.20	T
Polyphen		0.0020	B
Vest4		0.058
MutPred		0.58		Gain of methylation at K263 (P = 0.0252);
MVP		0.048
MPC		0.020
ClinPred		0.10	T
GERP RS		0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
gMVP		0.057

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: rs773036488; hg19: chr7-141464750;