7-143478036-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_176883.2(TAS2R41):c.164G>A(p.Arg55His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,613,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., 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: 1.87

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38889155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAS2R41	NM_176883.2	c.164G>A	p.Arg55His	missense_variant	1/1	ENST00000408916.1
EPHA1-AS1	NR_033897.1	n.207-26738G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAS2R41	ENST00000408916.1	c.164G>A	p.Arg55His	missense_variant	1/1		NM_176883.2	P1
EPHA1-AS1	ENST00000429289.5	n.207-26738G>A		intron_variant, non_coding_transcript_variant		1
EPHA1-AS1	ENST00000690912.1	n.228-17930G>A		intron_variant, non_coding_transcript_variant
EPHA1-AS1	ENST00000703017.1	n.206-17930G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0000855 AC: 13 AN: 152072 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.0000241 AC: 6 AN: 249250 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 135222

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000287 AC: 42 AN: 1461890 Hom.: 0 Cov.: 32 AF XY: 0.0000289 AC XY: 21 AN XY: 727246

Gnomad4 AFR exome AF: 0.0000896

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000333

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000855 AC: 13 AN: 152072 Hom.: 0 Cov.: 31 AF XY: 0.0000942 AC XY: 7 AN XY: 74274

Gnomad4 AFR AF: 0.000169

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.000116 Hom.: 0

Bravo AF: 0.000102

ESP6500AA AF: 0.000241 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000248 AC: 3

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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

Dec 06, 2023

The c.164G>A (p.R55H) alteration is located in exon 1 (coding exon 1) of the TAS2R41 gene. This alteration results from a G to A substitution at nucleotide position 164, causing the arginine (R) at amino acid position 55 to be replaced by a histidine (H). 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	0.26
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Uncertain	0.040
Cadd	Benign	22
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Benign	0.72	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.35	T
MutationAssessor	Pathogenic	3.4	M
MutationTaster	Benign	0.96	D
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.32
Sift	Benign	0.041	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.24
MVP		0.77
MPC		0.20
ClinPred		0.67	D
GERP RS		5.8
Varity_R		0.30
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs371558228; hg19: chr7-143175129;