6-78897869-T-C

Variant names:

• chr6-78897869-T-C
• NM_001010844.4:c.422T>C

Variant summary

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

The NM_001010844.4(IRAK1BP1):​c.422T>C​(p.Ile141Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: IRAK1BP1 NM_001010844.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.37

Genes affected

IRAK1BP1 (HGNC:17368): (interleukin 1 receptor associated kinase 1 binding protein 1) Predicted to be involved in I-kappaB kinase/NF-kappaB signaling. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRAK1BP1	NM_001010844.4	c.422T>C	p.Ile141Thr	missense_variant	Exon 3 of 4	ENST00000369940.7	NP_001010844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRAK1BP1	ENST00000369940.7	c.422T>C	p.Ile141Thr	missense_variant	Exon 3 of 4	1	NM_001010844.4	ENSP00000358956.1
IRAK1BP1	ENST00000606868.5	n.392T>C		non_coding_transcript_exon_variant	Exon 3 of 5	1		ENSP00000475570.1
IRAK1BP1	ENST00000607739.1	c.161T>C	p.Ile54Thr	missense_variant	Exon 3 of 5	2		ENSP00000475503.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 08, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.422T>C (p.I141T) alteration is located in exon 3 (coding exon 3) of the IRAK1BP1 gene. This alteration results from a T to C substitution at nucleotide position 422, causing the isoleucine (I) at amino acid position 141 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.0044	T
MetaRNN	Uncertain	0.62	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.8	D;.
REVEL	Benign	0.12
Sift	Benign	0.035	D;.
Sift4G	Benign	0.30	T;T
Polyphen		0.92	P;.
Vest4		0.87
MutPred		0.42		Loss of stability (P = 0.0809);.;
MVP		0.42
MPC		0.31
ClinPred		0.92	D
GERP RS		5.7
Varity_R		0.14
gMVP		0.37

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: chr6-79607586;