chr7-97739896-G-A
Position:
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_003182.3(TAC1):c.366G>A(p.Met122Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000137 in 1,604,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
TAC1
NM_003182.3 missense
NM_003182.3 missense
Scores
1
18
Clinical Significance
Conservation
PhyloP100: 5.23
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.085177064).
BS2
High AC in GnomAdExome4 at 18 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TAC1 | NM_003182.3 | c.366G>A | p.Met122Ile | missense_variant | 7/7 | ENST00000319273.10 | |
TAC1 | NM_013997.3 | c.321G>A | p.Met107Ile | missense_variant | 6/6 | ||
TAC1 | NM_013996.3 | c.312G>A | p.Met104Ile | missense_variant | 6/6 | ||
TAC1 | NM_013998.3 | c.267G>A | p.Met89Ile | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TAC1 | ENST00000319273.10 | c.366G>A | p.Met122Ile | missense_variant | 7/7 | 1 | NM_003182.3 | ||
TAC1 | ENST00000346867.4 | c.321G>A | p.Met107Ile | missense_variant | 6/6 | 3 | P1 | ||
TAC1 | ENST00000350485.8 | c.312G>A | p.Met104Ile | missense_variant | 6/6 | 5 | |||
TAC1 | ENST00000491437.1 | n.440G>A | non_coding_transcript_exon_variant | 4/4 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152058Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
4
AN:
152058
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.0000124 AC: 18AN: 1452414Hom.: 0 Cov.: 29 AF XY: 0.0000180 AC XY: 13AN XY: 722400
GnomAD4 exome
AF:
AC:
18
AN:
1452414
Hom.:
Cov.:
29
AF XY:
AC XY:
13
AN XY:
722400
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152058Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74268
GnomAD4 genome
AF:
AC:
4
AN:
152058
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
74268
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
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 | Oct 22, 2021 | The c.366G>A (p.M122I) alteration is located in exon 7 (coding exon 6) of the TAC1 gene. This alteration results from a G to A substitution at nucleotide position 366, causing the methionine (M) at amino acid position 122 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.
MutationTaster
Benign
D;D;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
B;B;B
Vest4
MutPred
Loss of disorder (P = 0.0378);.;.;
MVP
MPC
ClinPred
T
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