chr7-143478489-C-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_176883.2(TAS2R41):​c.617C>A​(p.Ser206Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

TAS2R41
NM_176883.2 missense

Scores

4
7
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.05
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.957

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TAS2R41NM_176883.2 linkc.617C>A p.Ser206Tyr missense_variant Exon 1 of 1 ENST00000408916.1 NP_795364.2 P59536
EPHA1-AS1NR_033897.1 linkn.207-26285C>A intron_variant Intron 2 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TAS2R41ENST00000408916.1 linkc.617C>A p.Ser206Tyr missense_variant Exon 1 of 1 6 NM_176883.2 ENSP00000386201.1 P59536
EPHA1-AS1ENST00000429289.5 linkn.207-26285C>A intron_variant Intron 2 of 4 1
EPHA1-AS1ENST00000690912.1 linkn.228-17477C>A intron_variant Intron 2 of 2
EPHA1-AS1ENST00000703017.1 linkn.206-17477C>A intron_variant Intron 2 of 2

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152082
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000201
AC:
5
AN:
249254
Hom.:
0
AF XY:
0.0000296
AC XY:
4
AN XY:
135238
show subpopulations
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:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000212
AC:
31
AN:
1461888
Hom.:
0
Cov.:
35
AF XY:
0.0000275
AC XY:
20
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000719
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152082
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74290
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.0000248
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.617C>A (p.S206Y) alteration is located in exon 1 (coding exon 1) of the TAS2R41 gene. This alteration results from a C to A substitution at nucleotide position 617, causing the serine (S) at amino acid position 206 to be replaced by a tyrosine (Y). 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
0.32
BayesDel_addAF
Uncertain
0.055
T
BayesDel_noAF
Uncertain
0.040
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.19
T
Eigen
Uncertain
0.44
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Uncertain
0.88
D
M_CAP
Benign
0.0071
T
MetaRNN
Pathogenic
0.96
D
MetaSVM
Benign
-0.96
T
MutationAssessor
Pathogenic
3.8
H
PrimateAI
Benign
0.44
T
PROVEAN
Pathogenic
-5.6
D
REVEL
Benign
0.26
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.0030
D
Polyphen
1.0
D
Vest4
0.78
MutPred
0.84
Gain of helix (P = 0.0349);
MVP
0.68
MPC
0.39
ClinPred
0.98
D
GERP RS
5.1
Varity_R
0.86
gMVP
0.27

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs750739454; hg19: chr7-143175582; API