chr18-58671692-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM2BP4_StrongBS1

The NM_006785.4(MALT1):c.49C>T(p.Pro17Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000319 in 1,254,808 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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: 33)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

MALT1
NM_006785.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.465

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 links:

MALT1-AS1 (HGNC:55306): (MALT1 antisense RNA 1)

MALT1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.031184673).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0000132 (2/151986) while in subpopulation SAS AF = 0.000414 (2/4830). AF 95% confidence interval is 0.0000729. There are 0 homozygotes in GnomAd4. There are 1 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006785.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MALT1	NM_006785.4	MANE Select	c.49C>T	p.Pro17Ser	missense	Exon 1 of 17	NP_006776.1	Q9UDY8-1
MALT1	NM_173844.3		c.49C>T	p.Pro17Ser	missense	Exon 1 of 16	NP_776216.1	Q9UDY8-2
MALT1-AS1	NR_164150.1		n.182G>A		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MALT1	ENST00000649217.2	MANE Select	c.49C>T	p.Pro17Ser	missense	Exon 1 of 17	ENSP00000497997.1	Q9UDY8-1
MALT1	ENST00000345724.7	TSL:1	c.49C>T	p.Pro17Ser	missense	Exon 1 of 16	ENSP00000304161.3	Q9UDY8-2
MALT1	ENST00000968608.1		c.49C>T	p.Pro17Ser	missense	Exon 1 of 18	ENSP00000638667.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151878

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000181

AC:

AN:

1102822

Hom.:

Cov.:

AF XY:

0.00000189

AC XY:

AN XY:

528208

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22706

American (AMR)

AF:

0.00

AC:

AN:

9440

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14578

East Asian (EAS)

AF:

0.00

AC:

AN:

25846

South Asian (SAS)

AF:

0.0000359

AC:

AN:

27892

European-Finnish (FIN)

AF:

0.00

AC:

AN:

22194

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2946

European-Non Finnish (NFE)

AF:

0.00000107

AC:

AN:

933456

Other (OTH)

AF:

0.00

AC:

AN:

43764

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151986

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41536

American (AMR)

AF:

0.00

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10482

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67932

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Combined immunodeficiency due to MALT1 deficiency (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.21

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0023

LIST_S2

Benign

0.51

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.031

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.71

PhyloP100

-0.47

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.19

REVEL

Benign

0.022

Sift

Benign

0.75

Sift4G

Benign

0.59

Polyphen

0.0

Vest4

0.051

MutPred

0.15

Gain of phosphorylation at P17 (P = 0.0252)

MVP

0.17

MPC

1.1

ClinPred

0.065

GERP RS

1.6

PromoterAI

0.0083

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.021

gMVP

0.56

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over