rs1172405267

Variant names:

• chr18-58671714-C-A
• rs1172405267
• NM_006785.4:c.71C>A

Your query was ambiguous. Multiple possible variants found:

• chr18-58671714-C-A
• chr18-58671714-C-G
• chr18-58671714-C-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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.277
• 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=0.14829114).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MALT1	NM_006785.4	c.71C>A	p.Pro24His	missense_variant	Exon 1 of 17	ENST00000649217.2	NP_006776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MALT1	ENST00000649217.2	c.71C>A	p.Pro24His	missense_variant	Exon 1 of 17		NM_006785.4	ENSP00000497997.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000178 AC: 2 AN: 1123812 Hom.: 0 Cov.: 31 AF XY: 0.00000185 AC XY: 1 AN XY: 541144

African (AFR) AF: 0.00 AC: 0 AN: 23120

American (AMR) AF: 0.00 AC: 0 AN: 11600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15570

East Asian (EAS) AF: 0.00 AC: 0 AN: 26040

South Asian (SAS) AF: 0.0000599 AC: 2 AN: 33372

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23136

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3042

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 943270

Other (OTH) AF: 0.00 AC: 0 AN: 44662

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T;T;.
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.42	.;T;T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;L;L
PhyloP100		0.28
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.0	N;.;N
REVEL	Benign	0.046
Sift	Uncertain	0.0020	D;.;D
Sift4G	Uncertain	0.0030	D;.;D
Polyphen		0.21	B;B;B
Vest4		0.15
MutPred		0.33		Gain of sheet (P = 4e-04);Gain of sheet (P = 4e-04);Gain of sheet (P = 4e-04);
MVP		0.18
MPC		1.4
ClinPred		0.77	D
GERP RS		3.6
PromoterAI		0.071	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.19
gMVP		0.38
Mutation Taster		=92/8	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: rs1172405267; hg19: chr18-56338946;