21-28945865-G-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_015565.3(LTN1):c.3710C>A(p.Ser1237Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,613,666 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. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
LTN1
NM_015565.3 missense
NM_015565.3 missense
Scores
1
18
Clinical Significance
Conservation
PhyloP100: 3.68
Genes affected
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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=0.14101267).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LTN1 | NM_015565.3 | c.3710C>A | p.Ser1237Tyr | missense_variant | 21/30 | ENST00000361371.10 | NP_056380.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LTN1 | ENST00000361371.10 | c.3710C>A | p.Ser1237Tyr | missense_variant | 21/30 | 1 | NM_015565.3 | ENSP00000354977.4 | ||
LTN1 | ENST00000614971.4 | c.3848C>A | p.Ser1283Tyr | missense_variant | 21/30 | 1 | ENSP00000478783.1 | |||
LTN1 | ENST00000389194.7 | c.3710C>A | p.Ser1237Tyr | missense_variant | 21/30 | 1 | ENSP00000373846.3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152162Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251152Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135732
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461504Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727046
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152162Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74338
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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 | Aug 08, 2023 | The c.3848C>A (p.S1283Y) alteration is located in exon 21 (coding exon 21) of the LTN1 gene. This alteration results from a C to A substitution at nucleotide position 3848, causing the serine (S) at amino acid position 1283 to be replaced by a tyrosine (Y). 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
Uncertain
D
LIST_S2
Benign
T;.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
PrimateAI
Benign
T
PROVEAN
Benign
N;N;.
REVEL
Benign
Sift
Benign
T;T;.
Sift4G
Benign
T;T;T
Polyphen
B;.;.
Vest4
MutPred
Gain of catalytic residue at L1232 (P = 0.0501);.;.;
MVP
MPC
0.31
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at