chr7-143444318-C-A

Position:

• chr7-143444318-C-A

Variant summary

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

The NM_177437.1(TAS2R60):​c.866C>A​(p.Ala289Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: TAS2R60 NM_177437.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.480

Genes affected

TAS2R60 (HGNC:20639): (taste 2 receptor member 60) 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. [provided by RefSeq, Jul 2017]

EPHA1-AS1 (HGNC:27799): (EPHA1 antisense RNA 1)

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=0.20070252).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAS2R60	NM_177437.1	c.866C>A	p.Ala289Glu	missense_variant	1/1	ENST00000332690.1
EPHA1-AS1	NR_033897.1	n.206+29119C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAS2R60	ENST00000332690.1	c.866C>A	p.Ala289Glu	missense_variant	1/1		NM_177437.1	P1
EPHA1-AS1	ENST00000429289.5	n.206+29119C>A		intron_variant, non_coding_transcript_variant		1
EPHA1-AS1	ENST00000690912.1	n.227+29119C>A		intron_variant, non_coding_transcript_variant
EPHA1-AS1	ENST00000703017.1	n.205+29119C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Feb 27, 2023

The c.866C>A (p.A289E) alteration is located in exon 1 (coding exon 1) of the TAS2R60 gene. This alteration results from a C to A substitution at nucleotide position 866, causing the alanine (A) at amino acid position 289 to be replaced by a glutamic acid (E). 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	0.28
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	6.6
DANN	Benign	0.88
DEOGEN2	Benign	0.0061	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.21	N
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.11
Sift	Benign	0.039	D
Sift4G	Benign	0.12	T
Polyphen		0.71	P
Vest4		0.31
MutPred		0.64		Loss of sheet (P = 0.1158);
MVP		0.41
MPC		0.34
ClinPred		0.18	T
GERP RS		-0.14
Varity_R		0.10
gMVP		0.31

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-143141411;