chr3-38138675-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002468.5(MYD88):​c.-26G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.1e-7 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

MYD88
NM_002468.5 5_prime_UTR

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.231
Variant links:
Genes affected
MYD88 (HGNC:7562): (MYD88 innate immune signal transduction adaptor) This gene encodes a cytosolic adapter protein that plays a central role in the innate and adaptive immune response. This protein functions as an essential signal transducer in the interleukin-1 and Toll-like receptor signaling pathways. These pathways regulate that activation of numerous proinflammatory genes. The encoded protein consists of an N-terminal death domain and a C-terminal Toll-interleukin1 receptor domain. Patients with defects in this gene have an increased susceptibility to pyogenic bacterial infections. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.075466335).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MYD88NM_002468.5 linkuse as main transcriptc.-26G>C 5_prime_UTR_variant 1/5 ENST00000650905.2 NP_002459.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MYD88ENST00000650905.2 linkuse as main transcriptc.-26G>C 5_prime_UTR_variant 1/5 NM_002468.5 ENSP00000498360 A1Q99836-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
7.07e-7
AC:
1
AN:
1415068
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
698404
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000242
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Pyogenic bacterial infections due to MyD88 deficiency Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpApr 11, 2021In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with MYD88-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with proline at codon 5 of the MYD88 protein (p.Arg5Pro). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and proline. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
7.7
DANN
Benign
0.78
DEOGEN2
Benign
0.012
T;.;.;.;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.40
N
LIST_S2
Benign
0.76
T;T;T;T;T
M_CAP
Benign
0.0066
T
MetaRNN
Benign
0.075
T;T;T;T;T
MetaSVM
Benign
-0.98
T
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-0.18
N;.;N;.;.
REVEL
Benign
0.021
Sift
Benign
0.11
T;.;D;.;.
Sift4G
Benign
0.25
T;.;T;.;.
Vest4
0.15
MutPred
0.14
Loss of methylation at R5 (P = 0.0294);Loss of methylation at R5 (P = 0.0294);Loss of methylation at R5 (P = 0.0294);Loss of methylation at R5 (P = 0.0294);Loss of methylation at R5 (P = 0.0294);
MVP
0.16
MPC
1.3
ClinPred
0.54
D
GERP RS
0.088

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-38180166; API