12-10802011-T-C

Variant names:

• chr12-10802011-T-C
• rs1320493994
• NM_023919.2:c.560A>G

Variant summary

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

The NM_023919.2(TAS2R7):​c.560A>G​(p.Asn187Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 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: 0.0000041 (0 hom.)
• Consequence: TAS2R7 NM_023919.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.151

Genes affected

TAS2R7 (HGNC:14913): (taste 2 receptor member 7) This gene product belongs to the family of candidate taste receptors that are members of the G-protein-coupled receptor superfamily. These proteins are specifically expressed in the taste receptor cells of the tongue and palate epithelia. They are organized in the genome in clusters and are genetically linked to loci that influence bitter perception in mice and humans. In functional expression studies, they respond to bitter tastants. This gene maps to the taste receptor gene cluster on chromosome 12p13. [provided by RefSeq, Jul 2008]

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, 0.794

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAS2R7	NM_023919.2	c.560A>G	p.Asn187Ser	missense_variant	Exon 1 of 1	ENST00000240687.2	NP_076408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAS2R7	ENST00000240687.2	c.560A>G	p.Asn187Ser	missense_variant	Exon 1 of 1	6	NM_023919.2	ENSP00000240687.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461640 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727094

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: 0.00000270

Gnomad4 OTH exome AF: 0.0000497

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.560A>G (p.N187S) alteration is located in exon 1 (coding exon 1) of the TAS2R7 gene. This alteration results from a A to G substitution at nucleotide position 560, causing the asparagine (N) at amino acid position 187 to be replaced by a serine (S). 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	0.20
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.010	T
Eigen	Benign	0.044
Eigen_PC	Benign	-0.016
FATHMM_MKL	Benign	0.29	N
M_CAP	Benign	0.0088	T
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.14
Sift	Benign	0.054	T
Sift4G	Benign	0.090	T
Polyphen		0.72	P
Vest4		0.62
MutPred		0.65		Gain of disorder (P = 0.1339);
MVP		0.29
MPC		0.018
ClinPred		0.91	D
GERP RS		5.3
Varity_R		0.26
gMVP		0.091

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1320493994; hg19: chr12-10954610; COSMIC: COSV105009088; COSMIC: COSV105009088;