dbSNP rs76121575: TACR3:p.Ser448Ser (chr4-103589736-G-A) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001059.3(TACR3):c.1344C>T(p.Ser448Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 1,613,912 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 57 hom. )

Consequence

TACR3
NM_001059.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.442

Publications

2 publications found

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 was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 4-103589736-G-A is Benign according to our data. Variant chr4-103589736-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 516718.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.442 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00216 (329/152246) while in subpopulation EAS AF = 0.053 (274/5166). AF 95% confidence interval is 0.0479. There are 6 homozygotes in GnomAd4. There are 176 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001059.3. 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
	TACR3	NM_001059.3	MANE Select	c.1344C>T	p.Ser448Ser	synonymous	Exon 5 of 5	NP_001050.1	P29371
	TACR3-AS1	NR_186501.1		n.190-1471G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TACR3	ENST00000304883.3	TSL:1 MANE Select	c.1344C>T	p.Ser448Ser	synonymous	Exon 5 of 5	ENSP00000303325.2	P29371
TACR3-AS1	ENST00000502936.1	TSL:2	n.190-1471G>A		intron	N/A
TACR3-AS1	ENST00000512401.5	TSL:2	n.292-1471G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00217

AC:

330

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.0533

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00443

AC:

1113

AN:

251156

AF XY:

0.00397

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.0560

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000529

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.00150

AC:

2188

AN:

1461666

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

1057

AN XY:

727126

show subpopulations

African (AFR)

AF:

0.000658

AC:

AN:

33460

American (AMR)

AF:

0.000157

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00138

AC:

AN:

26128

East Asian (EAS)

AF:

0.0470

AC:

1867

AN:

39686

South Asian (SAS)

AF:

0.00130

AC:

112

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000351

AC:

AN:

1111858

Other (OTH)

AF:

0.00174

AC:

105

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

149

298

448

597

746

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

144

180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00216

AC:

329

AN:

152246

Hom.:

Cov.:

AF XY:

0.00236

AC XY:

176

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.000746

AC:

AN:

41550

American (AMR)

AF:

0.000196

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3468

East Asian (EAS)

AF:

0.0530

AC:

274

AN:

5166

South Asian (SAS)

AF:

0.00228

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68028

Other (OTH)

AF:

0.00142

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000323

Hom.:

Bravo

AF:

0.00251

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Hypogonadotropic hypogonadism 11 with or without anosmia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

0.44

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over