NM_176817.5:c.645G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_176817.5(TAS2R38):​c.645G>A​(p.Met215Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000363 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 0.000036 ( 0 hom. )

Consequence

TAS2R38
NM_176817.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.05

Publications

0 publications found
Variant links:
Genes affected
TAS2R38 (HGNC:9584): (taste 2 receptor member 38) This gene encodes a seven-transmembrane G protein-coupled receptor that controls the ability to taste glucosinolates, a family of bitter-tasting compounds found in plants of the Brassica sp. Synthetic compounds phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) have been identified as ligands for this receptor and have been used to test the genetic diversity of this gene. Although several allelic forms of this gene have been identified worldwide, there are two predominant common forms (taster and non-taster) found outside of Africa. These alleles differ at three nucleotide positions resulting in amino acid changes in the protein (A49P, A262V, and V296I) with the amino acid combination PAV identifying the taster variant (and AVI identifying the non-taster variant). [provided by RefSeq, Oct 2009]
MGAM (HGNC:7043): (maltase-glucoamylase) This gene encodes maltase-glucoamylase, which is a brush border membrane enzyme that plays a role in the final steps of digestion of starch. The protein has two catalytic sites identical to those of sucrase-isomaltase, but the proteins are only 59% homologous. Both are members of glycosyl hydrolase family 31, which has a variety of substrate specificities. [provided by RefSeq, Jul 2008]
MGAM Gene-Disease associations (from GenCC):
  • Tourette syndrome
    Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.17074823).
BS2
High AC in GnomAdExome4 at 53 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TAS2R38NM_176817.5 linkc.645G>A p.Met215Ile missense_variant Exon 1 of 1 ENST00000547270.1 NP_789787.5 P59533

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TAS2R38ENST00000547270.1 linkc.645G>A p.Met215Ile missense_variant Exon 1 of 1 6 NM_176817.5 ENSP00000448219.1 P59533
MGAMENST00000465654.5 linkc.-3+27048C>T intron_variant Intron 2 of 5 3 ENSP00000419372.1 E7EW87

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
251238
AF XY:
0.00
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 FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000363
AC:
53
AN:
1461882
Hom.:
0
Cov.:
63
AF XY:
0.0000330
AC XY:
24
AN XY:
727244
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26134
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.0000187
AC:
1
AN:
53420
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.0000450
AC:
50
AN:
1112006
Other (OTH)
AF:
0.0000331
AC:
2
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.449
Heterozygous variant carriers
0
3
6
10
13
16
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.00000378
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 13, 2022
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.645G>A (p.M215I) alteration is located in exon 1 (coding exon 1) of the TAS2R38 gene. This alteration results from a G to A substitution at nucleotide position 645, causing the methionine (M) at amino acid position 215 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
0.18
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
12
DANN
Benign
0.80
DEOGEN2
Benign
0.0046
T
Eigen
Benign
-0.91
Eigen_PC
Benign
-0.91
FATHMM_MKL
Benign
0.087
N
LIST_S2
Uncertain
0.86
D
M_CAP
Benign
0.0072
T
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
1.4
L
PhyloP100
-1.1
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.070
N
REVEL
Benign
0.021
Sift
Benign
0.094
T
Sift4G
Benign
0.46
T
Polyphen
0.0090
B
Vest4
0.089
MutPred
0.63
Gain of catalytic residue at L220 (P = 0.0441);
MVP
0.092
MPC
0.23
ClinPred
0.054
T
GERP RS
0.82
Varity_R
0.12
gMVP
0.094
Mutation Taster
=98/2
polymorphism

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

Other links and lift over

dbSNP: rs782642723; hg19: chr7-141672845; API