Variant 4-103589609-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001059.3(TACR3):c.*73C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 1,574,150 control chromosomes in the GnomAD database, including 317,480 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 29952 hom., cov: 32)

Exomes 𝑓: 0.63 ( 287528 hom. )

Consequence

TACR3
NM_001059.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.302

Variant links:

Genes affected

TACR3 (HGNC:11528): (tachykinin receptor 3) 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 neurokinin 3, also referred to as neurokinin B. [provided by RefSeq, Jul 2008]

TACR3 links:

TACR3-AS1 (HGNC:55593): (TACR3 antisense RNA 1)

TACR3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 4-103589609-G-A is Benign according to our data. Variant chr4-103589609-G-A is described in ClinVar as [Benign]. Clinvar id is 347104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TACR3	NM_001059.3 linkuse as main transcript	c.*73C>T		3_prime_UTR_variant	5/5	ENST00000304883.3	NP_001050.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris
TACR3	ENST00000304883.3 linkuse as main transcript	c.*73C>T	3_prime_UTR_variant	5/5	1	NM_001059.3	ENSP00000303325	P1
TACR3-AS1	ENST00000502936.1 linkuse as main transcript	n.190-1598G>A	intron_variant, non_coding_transcript_variant		2
TACR3-AS1	ENST00000512401.5 linkuse as main transcript	n.292-1598G>A	intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.625

AC:

94849

AN:

151824

Hom.:

29928

Cov.:

show subpopulations

Gnomad AFR

AF:

0.592

Gnomad AMI

AF:

0.757

Gnomad AMR

AF:

0.625

Gnomad ASJ

AF:

0.645

Gnomad EAS

AF:

0.473

Gnomad SAS

AF:

0.439

Gnomad FIN

AF:

0.758

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.646

Gnomad OTH

AF:

0.618

GnomAD4 exome

AF:

0.632

AC:

898918

AN:

1422208

Hom.:

287528

Cov.:

AF XY:

0.627

AC XY:

444821

AN XY:

709524

show subpopulations

Gnomad4 AFR exome

AF:

0.588

Gnomad4 AMR exome

AF:

0.682

Gnomad4 ASJ exome

AF:

0.641

Gnomad4 EAS exome

AF:

0.477

Gnomad4 SAS exome

AF:

0.449

Gnomad4 FIN exome

AF:

0.747

Gnomad4 NFE exome

AF:

0.647

Gnomad4 OTH exome

AF:

0.611

GnomAD4 genome

AF:

0.625

AC:

94915

AN:

151942

Hom.:

29952

Cov.:

AF XY:

0.625

AC XY:

46398

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.592

Gnomad4 AMR

AF:

0.625

Gnomad4 ASJ

AF:

0.645

Gnomad4 EAS

AF:

0.472

Gnomad4 SAS

AF:

0.439

Gnomad4 FIN

AF:

0.758

Gnomad4 NFE

AF:

0.646

Gnomad4 OTH

AF:

0.618

Alfa

AF:

0.632

Hom.:

67926

Bravo

AF:

0.619

Asia WGS

AF:

0.475

AC:

1654

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hypogonadotropic hypogonadism 11 with or without anosmia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.35

DANN

Benign

0.29

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over