7-143443470-G-T

Position:

• chr7-143443470-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_177437.1(TAS2R60):​c.18G>T​(p.Met6Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000617 in 1,457,688 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: TAS2R60 NM_177437.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0740

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051100373).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAS2R60	NM_177437.1	c.18G>T	p.Met6Ile	missense_variant	1/1	ENST00000332690.1	NP_803186.1
EPHA1-AS1	NR_033897.1	n.206+28271G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAS2R60	ENST00000332690.1	c.18G>T	p.Met6Ile	missense_variant	1/1		NM_177437.1	ENSP00000327724	P1
EPHA1-AS1	ENST00000429289.5	n.206+28271G>T		intron_variant, non_coding_transcript_variant		1
EPHA1-AS1	ENST00000690912.1	n.227+28271G>T		intron_variant, non_coding_transcript_variant
EPHA1-AS1	ENST00000703017.1	n.205+28271G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000617 AC: 9 AN: 1457688 Hom.: 0 Cov.: 30 AF XY: 0.00000828 AC XY: 6 AN XY: 724792

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: 0.00000721

Gnomad4 OTH exome AF: 0.0000166

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

Jan 23, 2024

The c.18G>T (p.M6I) alteration is located in exon 1 (coding exon 1) of the TAS2R60 gene. This alteration results from a G to T substitution at nucleotide position 18, causing the methionine (M) at amino acid position 6 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	0.17
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.3
DANN	Benign	0.57
DEOGEN2	Benign	0.00084	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.058	N
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.0030
Sift	Benign	0.10	T
Sift4G	Benign	0.66	T
Polyphen		0.012	B
Vest4		0.052
MutPred		0.23		Gain of catalytic residue at M6 (P = 0.0441);
MVP		0.067
MPC		0.20
ClinPred		0.038	T
GERP RS		-1.9
Varity_R		0.079
gMVP		0.31

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: rs1806397586; hg19: chr7-143140563;