Genetic Variant NM_006785.4:c.42G>T (chr18-58671685-G-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_006785.4(MALT1):c.42G>T(p.Ser14Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S14S) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 9.1e-7 ( 0 hom. )

Consequence

MALT1
NM_006785.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.191

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: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP7

Synonymous conserved (PhyloP=-0.191 with no splicing effect.

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.42G>T	p.Ser14Ser	synonymous	Exon 1 of 17	NP_006776.1	Q9UDY8-1
MALT1	NM_173844.3		c.42G>T	p.Ser14Ser	synonymous	Exon 1 of 16	NP_776216.1	Q9UDY8-2
MALT1-AS1	NR_164150.1		n.189C>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.42G>T	p.Ser14Ser	synonymous	Exon 1 of 17	ENSP00000497997.1	Q9UDY8-1
MALT1	ENST00000345724.7	TSL:1	c.42G>T	p.Ser14Ser	synonymous	Exon 1 of 16	ENSP00000304161.3	Q9UDY8-2
MALT1	ENST00000968608.1		c.42G>T	p.Ser14Ser	synonymous	Exon 1 of 18	ENSP00000638667.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1097766

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

525084

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22622

American (AMR)

AF:

0.00

AC:

AN:

9078

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14292

East Asian (EAS)

AF:

0.00

AC:

AN:

25774

South Asian (SAS)

AF:

0.00

AC:

AN:

26768

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21934

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2904

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

930856

Other (OTH)

AF:

0.0000230

AC:

AN:

43538

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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

BayesDel_noAF

Benign

-0.75

CADD

Benign

9.0

(source)

DANN

Benign

0.83

PhyloP100

-0.19

PromoterAI

-0.037

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

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

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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