Variant 12-57013379-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013251.4(TAC3):c.218A>C(p.Glu73Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,772 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

TAC3
NM_013251.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.152

Variant links:

Genes affected

TAC3 (HGNC:11521): (tachykinin precursor 3) This gene encodes a member of the tachykinin family of secreted neuropeptides. The encoded preproprotein is proteolytically processed to generate the mature peptide, which is primarily expressed in the central and peripheral nervous systems and functions as a neurotransmitter. This peptide is the ligand for the neurokinin-3 receptor. This protein is also expressed in the outer syncytiotrophoblast of the placenta and may be associated with pregnancy-induced hypertension and pre-eclampsia. Mutations in this gene are associated with normosmic hypogonadotropic hypogonadism. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]

TAC3 links:

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ACMG classification

Classification made for transcript

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=0.10936725).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAC3	NM_013251.4 link	c.218A>C	p.Glu73Ala	missense_variant	Exon 4 of 7	ENST00000458521.7	NP_037383.1	Q9UHF0-1A0A024RB47

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TAC3	ENST00000458521.7 link	c.218A>C	p.Glu73Ala	missense_variant	Exon 4 of 7	1	NM_013251.4	ENSP00000404056.2	Q9UHF0-1
TAC3	ENST00000300108.7 link	n.218A>C		non_coding_transcript_exon_variant	Exon 4 of 9	2		ENSP00000300108.3	Q9UHF0-1
TAC3	ENST00000379411.6 link	n.218A>C		non_coding_transcript_exon_variant	Exon 4 of 8	2		ENSP00000368721.2	Q9UHF0-3
TAC3	ENST00000393867.5 link	n.218A>C		non_coding_transcript_exon_variant	Exon 4 of 10	2		ENSP00000377445.1	Q9UHF0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251448

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1461772

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727194

show subpopulations

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:

0.0000135

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000330

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.26

T;.;T;T

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.63

.;.;T;.

M_CAP

Benign

0.055

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-0.58

MutationAssessor

Benign

1.3

L;L;L;L

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.3

N;D;.;N

REVEL

Benign

0.12

Sift

Pathogenic

0.0

D;D;.;D

Sift4G

Benign

0.076

T;D;T;T

Polyphen

0.051

B;B;B;B

Vest4

0.19

MutPred

0.12

Loss of solvent accessibility (P = 0.0769);Loss of solvent accessibility (P = 0.0769);Loss of solvent accessibility (P = 0.0769);Loss of solvent accessibility (P = 0.0769);

MVP

0.71

MPC

1.5

ClinPred

0.13

GERP RS

2.2

Varity_R

0.087

gMVP

0.26

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over