rs5030920

Variant names:

• chr10-69416256-A-G
• rs5030920
• NM_001057.3:c.68T>C

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 22 publications found

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]

ENSG00000299486 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001057.3. 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
	TACR2	NM_001057.3	MANE Select	c.68T>C	p.Ile23Thr	missense	Exon 1 of 5	NP_001048.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TACR2	ENST00000373306.5	TSL:1 MANE Select	c.68T>C	p.Ile23Thr	missense	Exon 1 of 5	ENSP00000362403.4
	ENSG00000299486	ENST00000763854.1		n.85-8924A>G		intron	N/A

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

GnomAD2 exomes AF: 0.213 AC: 53553 AN: 251094 AF XY: 0.216

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 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

African (AFR) AF: 0.388 AC: 12980 AN: 33470

American (AMR) AF: 0.150 AC: 6716 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 5703 AN: 26122

East Asian (EAS) AF: 0.0224 AC: 889 AN: 39686

South Asian (SAS) AF: 0.287 AC: 24780 AN: 86224

European-Finnish (FIN) AF: 0.194 AC: 10302 AN: 53230

Middle Eastern (MID) AF: 0.262 AC: 1511 AN: 5764

European-Non Finnish (NFE) AF: 0.230 AC: 255154 AN: 1111496

Other (OTH) AF: 0.235 AC: 14191 AN: 60370

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

African (AFR) AF: 0.379 AC: 15732 AN: 41498

American (AMR) AF: 0.183 AC: 2798 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 806 AN: 3470

East Asian (EAS) AF: 0.0413 AC: 214 AN: 5184

South Asian (SAS) AF: 0.284 AC: 1368 AN: 4820

European-Finnish (FIN) AF: 0.183 AC: 1938 AN: 10600

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15426 AN: 67990

Other (OTH) AF: 0.243 AC: 514 AN: 2112

Alfa AF: 0.235 Hom.: 11847

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 v4.9

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
MetaRNN	Benign	0.0070	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.015
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.95	N
REVEL	Benign	0.019
Sift	Benign	0.64	T
Sift4G	Uncertain	0.0080	D
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
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5030920; hg19: chr10-71176012; COSMIC: COSV64822214;