3-38141146-C-A

Variant names:

• chr3-38141146-C-A
• rs748659894
• NM_002468.5:c.751C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001365876.1(MYD88):​c.732C>A​(p.Ser244Arg) variant causes a missense change. 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. Synonymous variant affecting the same amino acid position (i.e. S244S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MYD88 NM_001365876.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.77
• 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32423532).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365876.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYD88	NM_002468.5	MANE Select	c.751C>A	p.Arg251Arg	synonymous	Exon 5 of 5	NP_002459.3	Q99836-1
	MYD88	NM_001365876.1		c.732C>A	p.Ser244Arg	missense	Exon 5 of 5	NP_001352805.1	A0A494C0J8
	MYD88	NM_001374787.1		c.708C>A	p.Ser236Arg	missense	Exon 5 of 5	NP_001361716.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYD88	ENST00000650905.2	MANE Select	c.751C>A	p.Arg251Arg	synonymous	Exon 5 of 5	ENSP00000498360.2	Q99836-1
	MYD88	ENST00000421516.3	TSL:1	c.775C>A	p.Arg259Arg	synonymous	Exon 5 of 5	ENSP00000391753.3	Q99836-6
	MYD88	ENST00000417037.8	TSL:1	c.616C>A	p.Arg206Arg	synonymous	Exon 4 of 4	ENSP00000401399.4	Q99836-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Benign	12
DANN	Uncertain	1.0
Eigen	Benign	0.0054
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.93	T
PhyloP100		4.8
PROVEAN	Benign	0.090	N
REVEL	Benign	0.19
Sift	Pathogenic	0.0	D
Vest4		0.15
MutPred		0.12		Gain of MoRF binding (P = 0.0217)
MVP		0.44
ClinPred		0.94	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=35/65	disease causing

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: rs748659894; hg19: chr3-38182637;