rs1057520132
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_207037.2(TCF12):c.1490_1491delCT(p.Ser497CysfsTer12) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,672 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
TCF12
NM_207037.2 frameshift
NM_207037.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.437
Publications
0 publications found
Genes affected
TCF12 (HGNC:11623): (transcription factor 12) The protein encoded by this gene is a member of the basic helix-loop-helix (bHLH) E-protein family that recognizes the consensus binding site (E-box) CANNTG. This encoded protein is expressed in many tissues, among them skeletal muscle, thymus, B- and T-cells, and may participate in regulating lineage-specific gene expression through the formation of heterodimers with other bHLH E-proteins. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]
TCF12 Gene-Disease associations (from GenCC):
- TCF12-related craniosynostosisInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, ClinGen
- hypogonadotropic hypogonadism 26 with or without anosmiaInheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- Kallmann syndromeInheritance: AD, AR Classification: STRONG Submitted by: Franklin by Genoox
- isolated brachycephalyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- isolated plagiocephalyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 15-57262113-ACT-A is Pathogenic according to our data. Variant chr15-57262113-ACT-A is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 2582606.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_207037.2. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TCF12 | NM_207037.2 | MANE Select | c.1490_1491delCT | p.Ser497CysfsTer12 | frameshift | Exon 17 of 21 | NP_996920.1 | ||
| TCF12 | NM_001322151.2 | c.1490_1491delCT | p.Ser497CysfsTer12 | frameshift | Exon 17 of 21 | NP_001309080.1 | |||
| TCF12 | NM_001322159.3 | c.1490_1491delCT | p.Ser497CysfsTer12 | frameshift | Exon 17 of 21 | NP_001309088.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TCF12 | ENST00000333725.10 | TSL:1 MANE Select | c.1490_1491delCT | p.Ser497CysfsTer12 | frameshift | Exon 17 of 21 | ENSP00000331057.6 | ||
| TCF12 | ENST00000267811.9 | TSL:1 | c.1418_1419delCT | p.Ser473CysfsTer12 | frameshift | Exon 16 of 20 | ENSP00000267811.5 | ||
| TCF12 | ENST00000557843.5 | TSL:1 | c.1418_1419delCT | p.Ser473CysfsTer12 | frameshift | Exon 16 of 20 | ENSP00000453737.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460672Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 726640 show subpopulations
GnomAD4 exome
AF:
AC:
1
AN:
1460672
Hom.:
AF XY:
AC XY:
1
AN XY:
726640
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33438
American (AMR)
AF:
AC:
0
AN:
44606
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26084
East Asian (EAS)
AF:
AC:
0
AN:
39636
South Asian (SAS)
AF:
AC:
0
AN:
86062
European-Finnish (FIN)
AF:
AC:
0
AN:
53378
Middle Eastern (MID)
AF:
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
AC:
1
AN:
1111366
Other (OTH)
AF:
AC:
0
AN:
60338
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
ClinVar submissions as Germline
Significance:Pathogenic/Likely pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
1
-
-
Hypogonadotropic hypogonadism 26 with or without anosmia (1)
1
-
-
not provided (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
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
Publications
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