6-132588698-C-T

Variant names:

• chr6-132588698-C-T
• rs145127866
• NM_003967.3:c.989G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003967.3(TAAR5):​c.989G>A​(p.Arg330His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000864 in 1,612,926 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign 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. R330P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00091 (1 hom.)
• Consequence: TAAR5 NM_003967.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362
• Publications: 15 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.024672627).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003967.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAAR5	NM_003967.3	MANE Select	c.989G>A	p.Arg330His	missense	Exon 1 of 1	NP_003958.2	O14804
	TAAR5	NM_001389527.1		c.989G>A	p.Arg330His	missense	Exon 4 of 4	NP_001376456.1	O14804

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAAR5	ENST00000258034.4	TSL:6 MANE Select	c.989G>A	p.Arg330His	missense	Exon 1 of 1	ENSP00000258034.2	O14804

Frequencies

GnomAD3 genomes AF: 0.000395 AC: 60 AN: 152010 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000404 AC: 101 AN: 250110 AF XY: 0.000415

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000695

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000709

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000522

Gnomad OTH exome AF: 0.000328

GnomAD4 exome AF: 0.000913 AC: 1334 AN: 1460916 Hom.: 1 Cov.: 30 AF XY: 0.000867 AC XY: 630 AN XY: 726672

African (AFR) AF: 0.000179 AC: 6 AN: 33476

American (AMR) AF: 0.000671 AC: 30 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26048

East Asian (EAS) AF: 0.000605 AC: 24 AN: 39666

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86048

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00110 AC: 1223 AN: 1111520

Other (OTH) AF: 0.000795 AC: 48 AN: 60352

GnomAD4 genome AF: 0.000395 AC: 60 AN: 152010 Hom.: 0 Cov.: 31 AF XY: 0.000431 AC XY: 32 AN XY: 74240

African (AFR) AF: 0.000266 AC: 11 AN: 41378

American (AMR) AF: 0.000459 AC: 7 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000588 AC: 40 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000652 Hom.: 0

Bravo AF: 0.000412

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000930 AC: 8

ExAC AF: 0.000354 AC: 43

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00109

EpiControl AF: 0.000534

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.0077	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.36
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.34	N
REVEL	Benign	0.049
Sift	Benign	0.11	T
Sift4G	Benign	0.074	T
Polyphen		0.56	P
Vest4		0.13
MVP		0.52
MPC		0.013
ClinPred		0.012	T
GERP RS		2.6
Varity_R		0.028
gMVP		0.36
Mutation Taster		=99/1	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

Other links and lift over

dbSNP: rs145127866; hg19: chr6-132909837; COSMIC: COSV57798948;