ENST00000416282.3:n.42C>T

Variant names:

• chr3-38138692-C-T
• rs587778544
• ENST00000416282.3:n.42C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000416282.3(MYD88):​n.42C>T variant causes a non coding transcript exon 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MYD88 ENST00000416282.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.35
• Publications: 0 publications found

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]

MYD88 Gene-Disease associations (from GenCC):

• pyogenic bacterial infections due to MyD88 deficiency

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000299092 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06273723).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYD88	NM_002468.5	c.-9C>T		5_prime_UTR_variant	Exon 1 of 5	ENST00000650905.2	NP_002459.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYD88	ENST00000650905.2	c.-9C>T		5_prime_UTR_variant	Exon 1 of 5		NM_002468.5	ENSP00000498360.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.2
DANN	Benign	0.82
DEOGEN2	Benign	0.010	T;.;.;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.59	T;T;T;T;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.063	T;T;T;T;T
MetaSVM	Benign	-0.93	T
PhyloP100		-3.3
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.010	N;.;N;N;.
REVEL	Benign	0.013
Sift	Benign	0.51	T;.;T;D;.
Sift4G	Benign	0.58	T;.;T;.;.
Vest4		0.13
MutPred		0.19		Loss of catalytic residue at P11 (P = 0.0142);Loss of catalytic residue at P11 (P = 0.0142);Loss of catalytic residue at P11 (P = 0.0142);Loss of catalytic residue at P11 (P = 0.0142);Loss of catalytic residue at P11 (P = 0.0142);
MVP		0.21
MPC		0.58
ClinPred		0.11	T
GERP RS		0.21
PromoterAI		-0.050	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs587778544; hg19: chr3-38180183;