chr7-143478447-C-T

Variant summary

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

The NM_176883.2(TAS2R41):​c.575C>T​(p.Pro192Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P192H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 31)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

TAS2R41
NM_176883.2 missense

Scores

7
6
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.41
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, 0.981

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TAS2R41NM_176883.2 linkc.575C>T p.Pro192Leu missense_variant Exon 1 of 1 ENST00000408916.1 NP_795364.2 P59536
EPHA1-AS1NR_033897.1 linkn.207-26327C>T intron_variant Intron 2 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TAS2R41ENST00000408916.1 linkc.575C>T p.Pro192Leu missense_variant Exon 1 of 1 6 NM_176883.2 ENSP00000386201.1 P59536
EPHA1-AS1ENST00000429289.5 linkn.207-26327C>T intron_variant Intron 2 of 4 1
EPHA1-AS1ENST00000690912.1 linkn.228-17519C>T intron_variant Intron 2 of 2
EPHA1-AS1ENST00000703017.1 linkn.206-17519C>T intron_variant Intron 2 of 2

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
152014
Hom.:
0
Cov.:
31
FAILED QC
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:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461866
Hom.:
0
Cov.:
35
AF XY:
0.00000138
AC XY:
1
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
152132
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74372
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.52
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.17
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.095
T
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Benign
0.20
N
M_CAP
Benign
0.022
T
MetaRNN
Pathogenic
0.98
D
MetaSVM
Uncertain
-0.014
T
MutationAssessor
Pathogenic
3.2
M
PrimateAI
Benign
0.28
T
PROVEAN
Pathogenic
-9.9
D
REVEL
Uncertain
0.45
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.78
MutPred
0.91
Loss of catalytic residue at P192 (P = 0.0468);
MVP
0.78
MPC
0.36
ClinPred
1.0
D
GERP RS
6.0
Varity_R
0.87
gMVP
0.57

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-143175540; COSMIC: COSV68765253; API