chr4-166003554-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_012464.5(TLL1):c.796G>C(p.Glu266Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
TLL1
NM_012464.5 missense
NM_012464.5 missense
Scores
3
5
11
Clinical Significance
Conservation
PhyloP100: 10.0
Genes affected
TLL1 (HGNC:11843): (tolloid like 1) This gene encodes an astacin-like, zinc-dependent, metalloprotease that belongs to the peptidase M12A family. This protease processes procollagen C-propeptides, such as chordin, pro-biglycan and pro-lysyl oxidase. Studies in mice suggest that this gene plays multiple roles in the development of mammalian heart, and is essential for the formation of the interventricular septum. Allelic variants of this gene are associated with atrial septal defect type 6. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TLL1 | NM_012464.5 | c.796G>C | p.Glu266Gln | missense_variant | 6/21 | ENST00000061240.7 | |
TLL1 | NM_001204760.2 | c.796G>C | p.Glu266Gln | missense_variant | 6/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TLL1 | ENST00000061240.7 | c.796G>C | p.Glu266Gln | missense_variant | 6/21 | 1 | NM_012464.5 | P1 | |
TLL1 | ENST00000507499.5 | c.796G>C | p.Glu266Gln | missense_variant | 6/22 | 1 | |||
TLL1 | ENST00000513213.5 | c.796G>C | p.Glu266Gln | missense_variant | 6/10 | 1 | |||
TLL1 | ENST00000509505.5 | c.*441G>C | 3_prime_UTR_variant, NMD_transcript_variant | 6/21 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
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 | Jun 23, 2023 | The c.796G>C (p.E266Q) alteration is located in exon 6 (coding exon 6) of the TLL1 gene. This alteration results from a G to C substitution at nucleotide position 796, causing the glutamic acid (E) at amino acid position 266 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
D;D;D
Sift4G
Benign
T;T;T
Polyphen
P;P;.
Vest4
MutPred
Loss of catalytic residue at E266 (P = 0.0355);Loss of catalytic residue at E266 (P = 0.0355);Loss of catalytic residue at E266 (P = 0.0355);
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
Publications
No publications associated with this variant yet.