6-132645937-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_138327.4(TAAR1):​c.67C>T​(p.Arg23Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000916 in 1,612,494 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0042 ( 4 hom., cov: 32)
Exomes 𝑓: 0.00058 ( 2 hom. )

Consequence

TAAR1
NM_138327.4 missense

Scores

1
5
12

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.53
Variant links:
Genes affected
TAAR1 (HGNC:17734): (trace amine associated receptor 1) The protein encoded by this gene is a G-protein coupled receptor activated by trace amines. The encoded protein responds little or not at all to dopamine, serotonin, epinephrine, or histamine, but responds well to beta-phenylethylamine, p-tyramine, octopamine, and tryptamine. While primarily functioning in neurologic systems, there is evidence that this gene is involved in blood cell and immunologic functions as well. This gene is thought to be intronless. [provided by RefSeq, Nov 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.005964279).
BP6
Variant 6-132645937-G-A is Benign according to our data. Variant chr6-132645937-G-A is described in ClinVar as [Benign]. Clinvar id is 711978.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TAAR1NM_138327.4 linkc.67C>T p.Arg23Cys missense_variant 2/2 ENST00000275216.3 NP_612200.1 Q96RJ0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TAAR1ENST00000275216.3 linkc.67C>T p.Arg23Cys missense_variant 2/26 NM_138327.4 ENSP00000275216.1 Q96RJ0

Frequencies

GnomAD3 genomes
AF:
0.00420
AC:
639
AN:
152046
Hom.:
4
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0131
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00341
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.000382
Gnomad OTH
AF:
0.00621
GnomAD3 exomes
AF:
0.00128
AC:
320
AN:
249886
Hom.:
1
AF XY:
0.00111
AC XY:
150
AN XY:
134972
show subpopulations
Gnomad AFR exome
AF:
0.0138
Gnomad AMR exome
AF:
0.00143
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000331
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000319
Gnomad OTH exome
AF:
0.00164
GnomAD4 exome
AF:
0.000575
AC:
840
AN:
1460330
Hom.:
2
Cov.:
33
AF XY:
0.000504
AC XY:
366
AN XY:
726258
show subpopulations
Gnomad4 AFR exome
AF:
0.0129
Gnomad4 AMR exome
AF:
0.00150
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000233
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000212
Gnomad4 OTH exome
AF:
0.00138
GnomAD4 genome
AF:
0.00419
AC:
637
AN:
152164
Hom.:
4
Cov.:
32
AF XY:
0.00429
AC XY:
319
AN XY:
74396
show subpopulations
Gnomad4 AFR
AF:
0.0131
Gnomad4 AMR
AF:
0.00341
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000382
Gnomad4 OTH
AF:
0.00615
Alfa
AF:
0.00104
Hom.:
0
Bravo
AF:
0.00456
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000778
AC:
3
ESP6500AA
AF:
0.0129
AC:
57
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.00154
AC:
187
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.000416

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpApr 06, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.32
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.44
T
Eigen
Benign
-0.20
Eigen_PC
Benign
-0.17
FATHMM_MKL
Benign
0.46
N
LIST_S2
Benign
0.81
T
MetaRNN
Benign
0.0060
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.6
M
PrimateAI
Benign
0.24
T
PROVEAN
Pathogenic
-5.2
D
REVEL
Benign
0.064
Sift
Uncertain
0.025
D
Sift4G
Uncertain
0.0050
D
Polyphen
0.32
B
Vest4
0.29
MVP
0.46
MPC
0.011
ClinPred
0.055
T
GERP RS
4.7
Varity_R
0.17
gMVP
0.52

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

LitVar

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

Other links and lift over

dbSNP: rs8192618; hg19: chr6-132967076; API