X-154013099-G-T

Variant names:

• chrX-154013099-G-T
• NM_001569.4:c.1874C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001569.4(IRAK1):​c.1874C>A​(p.Thr625Lys) variant causes a missense 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. 14/20 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. T625M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 26)
• Consequence: IRAK1 NM_001569.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.425

Genes affected

IRAK1 (HGNC:6112): (interleukin 1 receptor associated kinase 1) This gene encodes the interleukin-1 receptor-associated kinase 1, one of two putative serine/threonine kinases that become associated with the interleukin-1 receptor (IL1R) upon stimulation. This gene is partially responsible for IL1-induced upregulation of the transcription factor NF-kappa B. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

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=0.09207484).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRAK1	NM_001569.4	c.1874C>A	p.Thr625Lys	missense_variant	Exon 12 of 14	ENST00000369980.8	NP_001560.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRAK1	ENST00000369980.8	c.1874C>A	p.Thr625Lys	missense_variant	Exon 12 of 14	1	NM_001569.4	ENSP00000358997.3

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.68
DEOGEN2	Benign	0.17	T;.;.;T
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.63	T;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.092	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.;.;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.9	N;N;N;N
REVEL	Benign	0.060
Sift	Benign	0.29	T;T;D;D
Sift4G	Benign	0.33	T;T;T;T
Polyphen		0.37	B;B;P;.
Vest4		0.11
MutPred		0.15		Gain of ubiquitination at T625 (P = 0.0054);.;.;.;
MVP		0.39
MPC		0.64
ClinPred		0.18	T
GERP RS		2.2
Varity_R		0.083
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chrX-153278550;