rs35533328
Positions:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1
The NM_006785.4(MALT1):āc.1921A>Gā(p.Ile641Val) variant causes a missense change. The variant allele was found at a frequency of 0.000309 in 1,612,442 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 Likely benign (ā ā ).
Frequency
Genomes: š 0.0017 ( 0 hom., cov: 32)
Exomes š: 0.00016 ( 0 hom. )
Consequence
MALT1
NM_006785.4 missense
NM_006785.4 missense
Scores
1
17
Clinical Significance
Conservation
PhyloP100: 3.88
Genes affected
MALT1 (HGNC:6819): (MALT1 paracaspase) This gene encodes a caspase-like protease that plays a role in BCL10-induced activation of NF-kappaB. The protein is a component of the CARMA1-BCL10-MALT1 (CBM) signalosome that triggers NF-kappaB signaling and lymphoctye activation following antigen-receptor stimulation. Mutations in this gene result in immunodeficiency 12 (IMD12). This gene has been found to be recurrently rearranged in chromosomal translocations with other genes in mucosa-associated lymphoid tissue lymphomas, including a t(11;18)(q21;q21) translocation with the baculoviral IAP repeat-containing protein 3 (also known as apoptosis inhibitor 2) locus [BIRC3(API2)-MALT1], and a t(14;18)(q32;q21) translocation with the immunoglobulin heavy chain locus (IGH-MALT1). Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, May 2018]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0038812459).
BP6
Variant 18-58745675-A-G is Benign according to our data. Variant chr18-58745675-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 474595.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00173 (263/152182) while in subpopulation AFR AF= 0.00621 (258/41524). AF 95% confidence interval is 0.00559. There are 0 homozygotes in gnomad4. There are 125 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MALT1 | NM_006785.4 | c.1921A>G | p.Ile641Val | missense_variant | 16/17 | ENST00000649217.2 | NP_006776.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MALT1 | ENST00000649217.2 | c.1921A>G | p.Ile641Val | missense_variant | 16/17 | NM_006785.4 | ENSP00000497997.1 |
Frequencies
GnomAD3 genomes AF: 0.00172 AC: 261AN: 152066Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000428 AC: 107AN: 250266Hom.: 0 AF XY: 0.000281 AC XY: 38AN XY: 135266
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GnomAD4 exome AF: 0.000162 AC: 236AN: 1460260Hom.: 0 Cov.: 31 AF XY: 0.000127 AC XY: 92AN XY: 726460
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GnomAD4 genome AF: 0.00173 AC: 263AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.00168 AC XY: 125AN XY: 74394
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Combined immunodeficiency due to MALT1 deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 11, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;T;T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;.
PrimateAI
Benign
T
PROVEAN
Benign
N;.;N
REVEL
Benign
Sift
Benign
T;.;T
Sift4G
Benign
T;.;T
Polyphen
B;B;B
Vest4
MVP
MPC
ClinPred
T
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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