6-132553114-C-T

Position:

• chr6-132553114-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_053278.3(TAAR8):​c.422C>T​(p.Thr141Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TAAR8 NM_053278.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.56

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11247426).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAAR8	NM_053278.3	c.422C>T	p.Thr141Ile	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.422C>T	p.Thr141Ile	missense_variant	1/1		NM_053278.3	ENSP00000275200	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2023

The c.422C>T (p.T141I) alteration is located in exon 1 (coding exon 1) of the TAAR8 gene. This alteration results from a C to T substitution at nucleotide position 422, causing the threonine (T) at amino acid position 141 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	10
DANN	Benign	0.95
DEOGEN2	Benign	0.086	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.019
Sift	Benign	0.085	T
Sift4G	Benign	0.15	T
Polyphen		0.0030	B
Vest4		0.053
MutPred		0.49		Gain of ubiquitination at K142 (P = 0.115);
MVP		0.19
MPC		0.037
ClinPred		0.17	T
GERP RS		2.0
Varity_R		0.13
gMVP		0.071

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: rs1776404854; hg19: chr6-132874253;