7-97736331-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_003182.3(TAC1):c.322G>A(p.Gly108Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,459,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
TAC1
NM_003182.3 missense
NM_003182.3 missense
Scores
10
7
2
Clinical Significance
Conservation
PhyloP100: 7.20
Genes affected
TAC1 (HGNC:11517): (tachykinin precursor 1) This gene encodes four products of the tachykinin peptide hormone family, substance P and neurokinin A, as well as the related peptides, neuropeptide K and neuropeptide gamma. These hormones are thought to function as neurotransmitters which interact with nerve receptors and smooth muscle cells. They are known to induce behavioral responses and function as vasodilators and secretagogues. Substance P is an antimicrobial peptide with antibacterial and antifungal properties. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.852
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TAC1 | NM_003182.3 | c.322G>A | p.Gly108Ser | missense_variant | 6/7 | ENST00000319273.10 | |
TAC1 | NM_013997.3 | c.277G>A | p.Gly93Ser | missense_variant | 5/6 | ||
TAC1 | NM_013996.3 | c.289+1482G>A | intron_variant | ||||
TAC1 | NM_013998.3 | c.244+1482G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TAC1 | ENST00000319273.10 | c.322G>A | p.Gly108Ser | missense_variant | 6/7 | 1 | NM_003182.3 | ||
TAC1 | ENST00000346867.4 | c.277G>A | p.Gly93Ser | missense_variant | 5/6 | 3 | P1 | ||
TAC1 | ENST00000350485.8 | c.289+1482G>A | intron_variant | 5 | |||||
TAC1 | ENST00000491437.1 | n.396G>A | non_coding_transcript_exon_variant | 3/4 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250330Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135428
GnomAD3 exomes
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1459378Hom.: 0 Cov.: 29 AF XY: 0.00000413 AC XY: 3AN XY: 726058
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GnomAD4 genome ? Cov.: 32
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?
Cov.:
32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 09, 2021 | The c.322G>A (p.G108S) alteration is located in exon 6 (coding exon 5) of the TAC1 gene. This alteration results from a G to A substitution at nucleotide position 322, causing the glycine (G) at amino acid position 108 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Pathogenic
D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Gain of disorder (P = 0.0566);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at