7-143478725-T-A

Variant summary

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

The NM_176883.2(TAS2R41):c.853T>A(p.Phe285Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000294 in 1,461,890 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: 31)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: TAS2R41 NM_176883.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.660

Genes affected

TAS2R41 (HGNC:18883): (taste 2 receptor member 41) 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. Chloramphenicol is an agonist for the encoded protein. [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=0.10396564).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAS2R41	NM_176883.2	c.853T>A	p.Phe285Ile	missense_variant	1/1	ENST00000408916.1
EPHA1-AS1	NR_033897.1	n.207-26049T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAS2R41	ENST00000408916.1	c.853T>A	p.Phe285Ile	missense_variant	1/1		NM_176883.2	P1
EPHA1-AS1	ENST00000429289.5	n.207-26049T>A		intron_variant, non_coding_transcript_variant		1
EPHA1-AS1	ENST00000690912.1	n.228-17241T>A		intron_variant, non_coding_transcript_variant
EPHA1-AS1	ENST00000703017.1	n.206-17241T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.0000121 AC: 3 AN: 248758 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 134930

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000267

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000294 AC: 43 AN: 1461890 Hom.: 0 Cov.: 35 AF XY: 0.0000385 AC XY: 28 AN XY: 727244

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: 0.0000387

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

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 01, 2023

The c.853T>A (p.F285I) alteration is located in exon 1 (coding exon 1) of the TAS2R41 gene. This alteration results from a T to A substitution at nucleotide position 853, causing the phenylalanine (F) at amino acid position 285 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	0.12
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	12
Dann	Benign	0.90
DEOGEN2	Benign	0.0021	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.032	N
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.2	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.18	N
REVEL	Benign	0.032
Sift	Benign	0.10	T
Sift4G	Benign	0.14	T
Polyphen		0.37	B
Vest4		0.24
MutPred		0.56		Gain of sheet (P = 0.0149);
MVP		0.092
MPC		0.12
ClinPred		0.080	T
GERP RS		-4.3
Varity_R		0.089
gMVP		0.065

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

LitVar

Other links and lift over

dbSNP: rs773580260; hg19: chr7-143175818;