NM_001394755.1:c.12G>T

Variant names:

• chr17-47696124-G-T
• NM_001394755.1:c.12G>T
• TBKBP1 p.Met4Ile

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394755.1(TBKBP1):​c.12G>T​(p.Met4Ile) 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. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TBKBP1 NM_001394755.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.54
• Publications: 0 publications found

Genes affected

TBKBP1 (HGNC:30140): (TBK1 binding protein 1) TBKBP1 is an adaptor protein that binds to TBK1 (MIM 604834) and is part of the interaction network in the TNF (MIM 191160)/NFKB (see MIM 164011) pathway (Bouwmeester et al., 2004 [PubMed 14743216]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20422265).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394755.1. 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
	TBKBP1	NM_001394755.1	MANE Select	c.12G>T	p.Met4Ile	missense	Exon 2 of 10	NP_001381684.1	A7MCY6-1
	TBKBP1	NM_001394756.1		c.12G>T	p.Met4Ile	missense	Exon 2 of 10	NP_001381685.1	A7MCY6-1
	TBKBP1	NM_014726.2		c.12G>T	p.Met4Ile	missense	Exon 1 of 9	NP_055541.1	A7MCY6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBKBP1	ENST00000578982.6	TSL:3 MANE Select	c.12G>T	p.Met4Ile	missense	Exon 2 of 10	ENSP00000462339.2	A7MCY6-1
	TBKBP1	ENST00000361722.7	TSL:1	c.12G>T	p.Met4Ile	missense	Exon 1 of 9	ENSP00000354777.3	A7MCY6-1
	TBKBP1	ENST00000851181.1		c.12G>T	p.Met4Ile	missense	Exon 2 of 10	ENSP00000521240.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.17
Eigen_PC	Benign	0.015
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		4.5
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.15
Sift	Benign	0.031	D
Sift4G	Benign	0.070	T
PromoterAI		-0.0080	Neutral
Varity_R		0.51
gMVP		0.21

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-45773490;