Genetic Variant NM_006785.4:c.71C>A (chr18-58671714-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006785.4(MALT1):c.71C>A(p.Pro24His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000178 in 1,123,812 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P24L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

MALT1
NM_006785.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.277

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14829114).

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.71C>A	p.Pro24His	missense	Exon 1 of 17	NP_006776.1	Q9UDY8-1
MALT1	NM_173844.3		c.71C>A	p.Pro24His	missense	Exon 1 of 16	NP_776216.1	Q9UDY8-2
MALT1-AS1	NR_164150.1		n.160G>T		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.71C>A	p.Pro24His	missense	Exon 1 of 17	ENSP00000497997.1	Q9UDY8-1
MALT1	ENST00000345724.7	TSL:1	c.71C>A	p.Pro24His	missense	Exon 1 of 16	ENSP00000304161.3	Q9UDY8-2
MALT1	ENST00000968608.1		c.71C>A	p.Pro24His	missense	Exon 1 of 18	ENSP00000638667.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000178

AC:

AN:

1123812

Hom.:

Cov.:

AF XY:

0.00000185

AC XY:

AN XY:

541144

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23120

American (AMR)

AF:

0.00

AC:

AN:

11600

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15570

East Asian (EAS)

AF:

0.00

AC:

AN:

26040

South Asian (SAS)

AF:

0.0000599

AC:

AN:

33372

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23136

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3042

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

943270

Other (OTH)

AF:

0.00

AC:

AN:

44662

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.24

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.42

M_CAP

Benign

0.059

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

0.28

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.0

REVEL

Benign

0.046

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

0.21

Vest4

0.15

MutPred

0.33

Gain of sheet (P = 4e-04)

MVP

0.18

MPC

1.4

ClinPred

0.77

GERP RS

3.6

PromoterAI

0.071

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.19

gMVP

0.38

Mutation Taster

=92/8

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