NM_006785.4:c.38C>T

Variant names:

• chr18-58671681-C-T
• rs2054162642
• NM_006785.4:c.38C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006785.4(MALT1):​c.38C>T​(p.Pro13Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000913 in 1,095,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 9.1e-7 (0 hom.)
• Consequence: MALT1 NM_006785.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.152
• Publications: 0 publications found

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)

ACMG classification

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=0.10296607).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MALT1	NM_006785.4	MANE Select	c.38C>T	p.Pro13Leu	missense	Exon 1 of 17	NP_006776.1	Q9UDY8-1
	MALT1	NM_173844.3		c.38C>T	p.Pro13Leu	missense	Exon 1 of 16	NP_776216.1	Q9UDY8-2
	MALT1-AS1	NR_164150.1		n.193G>A		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MALT1	ENST00000649217.2	MANE Select	c.38C>T	p.Pro13Leu	missense	Exon 1 of 17	ENSP00000497997.1	Q9UDY8-1
	MALT1	ENST00000345724.7	TSL:1	c.38C>T	p.Pro13Leu	missense	Exon 1 of 16	ENSP00000304161.3	Q9UDY8-2
	MALT1	ENST00000968608.1		c.38C>T	p.Pro13Leu	missense	Exon 1 of 18	ENSP00000638667.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.13e-7 AC: 1 AN: 1095342 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 523570

African (AFR) AF: 0.0000443 AC: 1 AN: 22568

American (AMR) AF: 0.00 AC: 0 AN: 8842

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14160

East Asian (EAS) AF: 0.00 AC: 0 AN: 25740

South Asian (SAS) AF: 0.00 AC: 0 AN: 26180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21852

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2900

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 929672

Other (OTH) AF: 0.00 AC: 0 AN: 43428

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Combined immunodeficiency due to MALT1 deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.0033	N
LIST_S2	Benign	0.63	T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.15
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.054
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.028	D
Polyphen		0.079	B
Vest4		0.088
MutPred		0.22		Loss of glycosylation at P13 (P = 0.0166)
MVP		0.28
MPC		0.51
ClinPred		0.28	T
GERP RS		3.5
PromoterAI		-0.025	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.10
gMVP		0.62
Mutation Taster		=94/6	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

Other links and lift over

dbSNP: rs2054162642; hg19: chr18-56338913;