chr6-132553675-A-C

Position:

• chr6-132553675-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_053278.3(TAAR8):​c.983A>C​(p.Asp328Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0665 in 1,609,538 control chromosomes in the GnomAD database, including 3,983 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 0.056 (320 hom., cov: 32)
  • Exomes 𝑓: 0.068 (3663 hom.)
• Consequence: TAAR8 NM_053278.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45

Genes affected

TAAR8 (HGNC:14964): (trace amine associated receptor 8) This gene is part of the trace amine receptor cluster on chromosome 6 and encodes an orphan G-protein coupled receptor. Upregulated expression of this gene in astroglial cells upon exposure to lipopolysaccharides suggests a function for the encoded protein in the brain. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0019015968).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAAR8	NM_053278.3	c.983A>C	p.Asp328Ala	missense_variant	1/1	ENST00000275200.2	NP_444508.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAAR8	ENST00000275200.2	c.983A>C	p.Asp328Ala	missense_variant	1/1	6	NM_053278.3	ENSP00000275200.1

Frequencies

GnomAD3 genomes AF: 0.0564 AC: 8575 AN: 152136 Hom.: 318 Cov.: 32

Gnomad AFR AF: 0.0282

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0377

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.0106

Gnomad SAS AF: 0.0461

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0750

Gnomad OTH AF: 0.0464

GnomAD3 exomes AF: 0.0573 AC: 14186 AN: 247436 Hom.: 506 AF XY: 0.0587 AC XY: 7847 AN XY: 133728

Gnomad AFR exome AF: 0.0294

Gnomad AMR exome AF: 0.0235

Gnomad ASJ exome AF: 0.0213

Gnomad EAS exome AF: 0.00790

Gnomad SAS exome AF: 0.0462

Gnomad FIN exome AF: 0.114

Gnomad NFE exome AF: 0.0744

Gnomad OTH exome AF: 0.0646

GnomAD4 exome AF: 0.0676 AC: 98522 AN: 1457284 Hom.: 3663 Cov.: 31 AF XY: 0.0672 AC XY: 48722 AN XY: 724654

Gnomad4 AFR exome AF: 0.0286

Gnomad4 AMR exome AF: 0.0248

Gnomad4 ASJ exome AF: 0.0204

Gnomad4 EAS exome AF: 0.0101

Gnomad4 SAS exome AF: 0.0454

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.0736

Gnomad4 OTH exome AF: 0.0587

GnomAD4 genome AF: 0.0564 AC: 8589 AN: 152254 Hom.: 320 Cov.: 32 AF XY: 0.0562 AC XY: 4186 AN XY: 74432

Gnomad4 AFR AF: 0.0283

Gnomad4 AMR AF: 0.0377

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.0106

Gnomad4 SAS AF: 0.0460

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.0750

Gnomad4 OTH AF: 0.0487

Alfa AF: 0.0650 Hom.: 886

Bravo AF: 0.0485

TwinsUK AF: 0.0728 AC: 270

ALSPAC AF: 0.0752 AC: 290

ESP6500AA AF: 0.0272 AC: 120

ESP6500EA AF: 0.0719 AC: 618

ExAC AF: 0.0581 AC: 7054

Asia WGS AF: 0.0300 AC: 103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	8.5
DANN	Benign	0.94
DEOGEN2	Benign	0.0045	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.13
Sift	Uncertain	0.011	D
Sift4G	Benign	0.061	T
Polyphen		0.0020	B
Vest4		0.032
MPC		0.039
ClinPred		0.0071	T
GERP RS		0.63
Varity_R		0.078
gMVP		0.067

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs8192627; hg19: chr6-132874814; COSMIC: COSV51586114;