18-58671652-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_006785.4(MALT1):​c.9G>T​(p.Leu3Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,218,716 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 7 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 29 hom. )

Consequence

MALT1
NM_006785.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0310

Publications

0 publications found
Variant links:
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]
MALT1-AS1 (HGNC:55306): (MALT1 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
Variant 18-58671652-G-T is Benign according to our data. Variant chr18-58671652-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1160393.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.031 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00153 (232/151974) while in subpopulation SAS AF = 0.0456 (220/4828). AF 95% confidence interval is 0.0406. There are 7 homozygotes in GnomAd4. There are 159 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MALT1NM_006785.4 linkc.9G>T p.Leu3Leu synonymous_variant Exon 1 of 17 ENST00000649217.2 NP_006776.1 Q9UDY8-1A8K5S1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MALT1ENST00000649217.2 linkc.9G>T p.Leu3Leu synonymous_variant Exon 1 of 17 NM_006785.4 ENSP00000497997.1 Q9UDY8-1

Frequencies

GnomAD3 genomes
AF:
0.00153
AC:
233
AN:
151866
Hom.:
7
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000656
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0457
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000442
Gnomad OTH
AF:
0.000480
GnomAD2 exomes
AF:
0.00725
AC:
1
AN:
138
AF XY:
0.0106
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00113
AC:
1208
AN:
1066742
Hom.:
29
Cov.:
31
AF XY:
0.00133
AC XY:
673
AN XY:
504422
show subpopulations
African (AFR)
AF:
0.000135
AC:
3
AN:
22222
American (AMR)
AF:
0.000257
AC:
2
AN:
7796
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
13490
East Asian (EAS)
AF:
0.000119
AC:
3
AN:
25208
South Asian (SAS)
AF:
0.0508
AC:
1029
AN:
20240
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
20920
Middle Eastern (MID)
AF:
0.000708
AC:
2
AN:
2826
European-Non Finnish (NFE)
AF:
0.0000658
AC:
60
AN:
911664
Other (OTH)
AF:
0.00257
AC:
109
AN:
42376
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.470
Heterozygous variant carriers
0
63
125
188
250
313
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
38
76
114
152
190
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00153
AC:
232
AN:
151974
Hom.:
7
Cov.:
32
AF XY:
0.00214
AC XY:
159
AN XY:
74298
show subpopulations
African (AFR)
AF:
0.000169
AC:
7
AN:
41522
American (AMR)
AF:
0.0000655
AC:
1
AN:
15268
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5168
South Asian (SAS)
AF:
0.0456
AC:
220
AN:
4828
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10472
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
292
European-Non Finnish (NFE)
AF:
0.0000442
AC:
3
AN:
67938
Other (OTH)
AF:
0.000475
AC:
1
AN:
2104
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.505
Heterozygous variant carriers
0
11
22
32
43
54
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.000139
Hom.:
0
Bravo
AF:
0.000283
Asia WGS
AF:
0.0210
AC:
73
AN:
3432

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
Jan 24, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.59
CADD
Benign
13
DANN
Benign
0.60
PhyloP100
0.031
PromoterAI
-0.018
Neutral
Mutation Taster
=100/0
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs373689542; hg19: chr18-56338884; API