18-6213231-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001330559.2(L3MBTL4):c.899T>C(p.Met300Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000745 in 1,609,890 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000069 ( 0 hom. )
Consequence
L3MBTL4
NM_001330559.2 missense
NM_001330559.2 missense
Scores
2
9
8
Clinical Significance
Conservation
PhyloP100: 5.91
Genes affected
L3MBTL4 (HGNC:26677): (L3MBTL histone methyl-lysine binding protein 4) Predicted to enable chromatin binding activity and histone binding activity. Predicted to be involved in negative regulation of transcription, DNA-templated. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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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 |
---|---|---|---|---|---|---|---|
L3MBTL4 | NM_001330559.2 | c.899T>C | p.Met300Thr | missense_variant | 12/19 | ENST00000317931.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
L3MBTL4 | ENST00000317931.12 | c.899T>C | p.Met300Thr | missense_variant | 12/19 | 5 | NM_001330559.2 | P4 | |
L3MBTL4 | ENST00000400104.7 | c.899T>C | p.Met300Thr | missense_variant | 12/17 | 1 | |||
L3MBTL4 | ENST00000400105.6 | c.899T>C | p.Met300Thr | missense_variant | 12/20 | 2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152192Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000242 AC: 6AN: 247560Hom.: 0 AF XY: 0.0000374 AC XY: 5AN XY: 133524
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GnomAD4 exome AF: 0.00000686 AC: 10AN: 1457698Hom.: 0 Cov.: 29 AF XY: 0.00000966 AC XY: 7AN XY: 724808
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152192Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74356
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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 | Mar 24, 2023 | The c.899T>C (p.M300T) alteration is located in exon 12 (coding exon 10) of the L3MBTL4 gene. This alteration results from a T to C substitution at nucleotide position 899, causing the methionine (M) at amino acid position 300 to be replaced by a threonine (T). 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
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.;M
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
T;T;T
Polyphen
B;B;.
Vest4
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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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