rs5030920

Positions:

• chr10-69416256-A-G

Variant summary

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

The NM_001057.3(TACR2):​c.68T>C​(p.Ile23Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,613,236 control chromosomes in the GnomAD database, including 45,413 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 0.26 (5661 hom., cov: 33)
  • Exomes 𝑓: 0.23 (39752 hom.)
• Consequence: TACR2 NM_001057.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150

Genes affected

TACR2 (HGNC:11527): (tachykinin receptor 2) This gene belongs to a family of genes that function as receptors for tachykinins. Receptor affinities are specified by variations in the 5'-end of the sequence. The receptors belonging to this family are characterized by interactions with G proteins and 7 hydrophobic transmembrane regions. This gene encodes the receptor for the tachykinin neuropeptide substance K, also referred to as neurokinin A. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007045418).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACR2	NM_001057.3	c.68T>C	p.Ile23Thr	missense_variant	1/5	ENST00000373306.5	NP_001048.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TACR2	ENST00000373306.5	c.68T>C	p.Ile23Thr	missense_variant	1/5	1	NM_001057.3	ENSP00000362403.4

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38986 AN: 152052 Hom.: 5665 Cov.: 33

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.0412

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.245

GnomAD3 exomes AF: 0.213 AC: 53553 AN: 251094 Hom.: 6476 AF XY: 0.216 AC XY: 29369 AN XY: 135736

Gnomad AFR exome AF: 0.378

Gnomad AMR exome AF: 0.142

Gnomad ASJ exome AF: 0.217

Gnomad EAS exome AF: 0.0386

Gnomad SAS exome AF: 0.287

Gnomad FIN exome AF: 0.191

Gnomad NFE exome AF: 0.224

Gnomad OTH exome AF: 0.206

GnomAD4 exome AF: 0.227 AC: 332226 AN: 1461066 Hom.: 39752 Cov.: 34 AF XY: 0.229 AC XY: 166113 AN XY: 726708

Gnomad4 AFR exome AF: 0.388

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 0.218

Gnomad4 EAS exome AF: 0.0224

Gnomad4 SAS exome AF: 0.287

Gnomad4 FIN exome AF: 0.194

Gnomad4 NFE exome AF: 0.230

Gnomad4 OTH exome AF: 0.235

GnomAD4 genome AF: 0.256 AC: 39007 AN: 152170 Hom.: 5661 Cov.: 33 AF XY: 0.250 AC XY: 18632 AN XY: 74406

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.0413

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.183

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.243

Alfa AF: 0.229 Hom.: 8103

Bravo AF: 0.257

TwinsUK AF: 0.227 AC: 842

ALSPAC AF: 0.238 AC: 916

ESP6500AA AF: 0.374 AC: 1649

ESP6500EA AF: 0.224 AC: 1930

ExAC AF: 0.221 AC: 26841

Asia WGS AF: 0.163 AC: 569 AN: 3478

EpiCase AF: 0.228

EpiControl AF: 0.226

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.3
DANN	Benign	0.33
DEOGEN2	Benign	0.018	.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.15	T;T
MetaRNN	Benign	0.0070	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.6	.;L
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.95	.;N
REVEL	Benign	0.019
Sift	Benign	0.64	.;T
Sift4G	Uncertain	0.0080	D;T
Polyphen		0.0	.;B
Vest4		0.016
MPC		0.34
ClinPred		0.00088	T
GERP RS		2.8
Varity_R		0.019
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs5030920; hg19: chr10-71176012; COSMIC: COSV64822214;