3-38138693-C-T

Variant names:

• chr3-38138693-C-T
• ENST00000650905:c.-8C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002468.5(MYD88):​c.-8C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,670 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.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MYD88 NM_002468.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034140646).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYD88	NM_002468.5	c.-8C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 5	ENST00000650905.2	NP_002459.3
MYD88	NM_002468.5	c.-8C>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	c.-8C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 5		NM_002468.5	ENSP00000498360.2
MYD88	ENST00000650905	c.-8C>T		5_prime_UTR_variant	Exon 1 of 5		NM_002468.5	ENSP00000498360.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444670 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 716530

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 9.07e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.49
DANN	Benign	0.89
DEOGEN2	Benign	0.010	T;.;.;T;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.48	T;T;T;T;T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.034	T;T;T;T;T
MetaSVM	Benign	-0.93	T
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	0.18	N;.;N;N;.
REVEL	Benign	0.016
Sift	Benign	1.0	T;.;T;D;.
Sift4G	Benign	0.90	T;.;T;.;.
Vest4		0.16
MutPred		0.20		Loss of glycosylation at P11 (P = 0.0173);Loss of glycosylation at P11 (P = 0.0173);Loss of glycosylation at P11 (P = 0.0173);Loss of glycosylation at P11 (P = 0.0173);Loss of glycosylation at P11 (P = 0.0173);
MVP		0.12
MPC		0.63
ClinPred		0.039	T
GERP RS		-4.9
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-38180184; COSMIC: COSV57179685; COSMIC: COSV57179685;