rs9389004

Variant names:

• chr6-132539121-G-A
• rs9389004
• NM_175057.4:c.832G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_175057.4(TAAR9):​c.832G>A​(p.Ala278Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 1,563,556 control chromosomes in the GnomAD database, including 1,818 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/13 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.037 (160 hom., cov: 32)
  • Exomes 𝑓: 0.046 (1658 hom.)
• Consequence: TAAR9 NM_175057.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.509

Genes affected

TAAR9 (HGNC:20977): (trace amine associated receptor 9) TAAR9 is a member of a large family of rhodopsin G protein-coupled receptors (GPCRs, or GPRs). GPCRs contain 7 transmembrane domains and transduce extracellular signals through heterotrimeric G proteins.[supplied by OMIM, Jul 2005]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019289851).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0372 (5658/152276) while in subpopulation NFE AF= 0.0514 (3494/68010). AF 95% confidence interval is 0.05. There are 160 homozygotes in gnomad4. There are 2839 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 160 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAAR9	NM_175057.4	c.832G>A	p.Ala278Thr	missense_variant	Exon 1 of 1	ENST00000434551.3	NP_778227.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAAR9	ENST00000434551.3	c.832G>A	p.Ala278Thr	missense_variant	Exon 1 of 1	6	NM_175057.4	ENSP00000424607.2

Frequencies

GnomAD3 genomes AF: 0.0372 AC: 5654 AN: 152158 Hom.: 160 Cov.: 32

Gnomad AFR AF: 0.00789

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0259

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.0317

Gnomad FIN AF: 0.0927

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0514

Gnomad OTH AF: 0.0311

GnomAD3 exomes AF: 0.0403 AC: 7860 AN: 195240 Hom.: 198 AF XY: 0.0413 AC XY: 4328 AN XY: 104918

Gnomad AFR exome AF: 0.00896

Gnomad AMR exome AF: 0.0174

Gnomad ASJ exome AF: 0.0162

Gnomad EAS exome AF: 0.00766

Gnomad SAS exome AF: 0.0342

Gnomad FIN exome AF: 0.0914

Gnomad NFE exome AF: 0.0490

Gnomad OTH exome AF: 0.0462

GnomAD4 exome AF: 0.0457 AC: 64533 AN: 1411280 Hom.: 1658 Cov.: 33 AF XY: 0.0457 AC XY: 31909 AN XY: 698614

Gnomad4 AFR exome AF: 0.00736

Gnomad4 AMR exome AF: 0.0183

Gnomad4 ASJ exome AF: 0.0160

Gnomad4 EAS exome AF: 0.0101

Gnomad4 SAS exome AF: 0.0343

Gnomad4 FIN exome AF: 0.0937

Gnomad4 NFE exome AF: 0.0484

Gnomad4 OTH exome AF: 0.0414

GnomAD4 genome AF: 0.0372 AC: 5658 AN: 152276 Hom.: 160 Cov.: 32 AF XY: 0.0381 AC XY: 2839 AN XY: 74458

Gnomad4 AFR AF: 0.00787

Gnomad4 AMR AF: 0.0260

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.0104

Gnomad4 SAS AF: 0.0315

Gnomad4 FIN AF: 0.0927

Gnomad4 NFE AF: 0.0514

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.0432 Hom.: 221

Bravo AF: 0.0303

TwinsUK AF: 0.0520 AC: 193

ALSPAC AF: 0.0485 AC: 187

ESP6500AA AF: 0.00958 AC: 36

ESP6500EA AF: 0.0488 AC: 401

ExAC AF: 0.0378 AC: 4561

Asia WGS AF: 0.0210 AC: 72 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	12
DANN	Benign	0.37
DEOGEN2	Benign	0.013	T
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.0019	T
MutationAssessor	Benign	-0.56	N
PrimateAI	Benign	0.29	T
Sift4G	Benign	1.0	T
Polyphen		0.0030	B
Vest4		0.031
GERP RS		1.3
Varity_R		0.099
gMVP		0.065

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

LitVar

Other links and lift over

dbSNP: rs9389004; hg19: chr6-132860260;