6-132588699-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003967.3(TAAR5):c.988C>T(p.Arg330Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00569 in 1,613,532 control chromosomes in the GnomAD database, including 417 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R330P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.028 (194 hom., cov: 31)
  • Exomes 𝑓: 0.0034 (223 hom.)
• Consequence: TAAR5 NM_003967.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.127

Genes affected

TAAR5 (HGNC:30236): (trace amine associated receptor 5) Enables trimethylamine receptor activity. Predicted to be involved in signal transduction. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016864836).
• BP6: Variant 6-132588699-G-A is Benign according to our data. Variant chr6-132588699-G-A is described in ClinVar as [Benign]. Clinvar id is 783474.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAAR5	NM_003967.3	c.988C>T	p.Arg330Cys	missense_variant	1/1	ENST00000258034.4
TAAR5	NM_001389527.1	c.988C>T	p.Arg330Cys	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAAR5	ENST00000258034.4	c.988C>T	p.Arg330Cys	missense_variant	1/1		NM_003967.3	P1

Frequencies

GnomAD3 genomes AF: 0.0280 AC: 4261 AN: 151978 Hom.: 193 Cov.: 31

Gnomad AFR AF: 0.0975

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00969

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000485

Gnomad OTH AF: 0.0230

GnomAD3 exomes AF: 0.00758 AC: 1899 AN: 250602 Hom.: 96 AF XY: 0.00555 AC XY: 752 AN XY: 135404

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.00501

Gnomad ASJ exome AF: 0.000200

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000548

Gnomad OTH exome AF: 0.00360

GnomAD4 exome AF: 0.00336 AC: 4909 AN: 1461436 Hom.: 223 Cov.: 30 AF XY: 0.00290 AC XY: 2109 AN XY: 727004

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.00557

Gnomad4 ASJ exome AF: 0.000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000555

Gnomad4 OTH exome AF: 0.00689

GnomAD4 genome AF: 0.0281 AC: 4276 AN: 152096 Hom.: 194 Cov.: 31 AF XY: 0.0268 AC XY: 1997 AN XY: 74378

Gnomad4 AFR AF: 0.0976

Gnomad4 AMR AF: 0.00968

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000485

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.00498 Hom.: 39

Bravo AF: 0.0314

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.0885 AC: 390

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.00903 AC: 1097

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.58
Cadd	Benign	18
Dann	Benign	0.90
DEOGEN2	Benign	0.0052	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.26	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.53	N
REVEL	Benign	0.077
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.020	D
Polyphen		0.0010	B
Vest4		0.11
MVP		0.43
MPC		0.012
ClinPred		0.0071	T
GERP RS		0.28
Varity_R		0.071
gMVP		0.41

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

Other links and lift over

dbSNP: rs35839363; hg19: chr6-132909838;