17-47698650-G-A

Variant names:

• chr17-47698650-G-A
• rs181655124
• NM_001394755.1:c.509G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001394755.1(TBKBP1):​c.509G>A​(p.Arg170Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000168 in 1,602,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. R170L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: TBKBP1 NM_001394755.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.23
• Publications: 3 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010171711).

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.509G>A	p.Arg170Gln	missense	Exon 5 of 10	NP_001381684.1	A7MCY6-1
	TBKBP1	NM_001394756.1		c.509G>A	p.Arg170Gln	missense	Exon 5 of 10	NP_001381685.1	A7MCY6-1
	TBKBP1	NM_014726.2		c.509G>A	p.Arg170Gln	missense	Exon 4 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.509G>A	p.Arg170Gln	missense	Exon 5 of 10	ENSP00000462339.2	A7MCY6-1
	TBKBP1	ENST00000361722.7	TSL:1	c.509G>A	p.Arg170Gln	missense	Exon 4 of 9	ENSP00000354777.3	A7MCY6-1
	TBKBP1	ENST00000851181.1		c.509G>A	p.Arg170Gln	missense	Exon 5 of 10	ENSP00000521240.1

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 152126 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000197 AC: 45 AN: 227862 AF XY: 0.000211

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000210

Gnomad EAS exome AF: 0.00187

Gnomad FIN exome AF: 0.0000494

Gnomad NFE exome AF: 0.0000684

Gnomad OTH exome AF: 0.000530

GnomAD4 exome AF: 0.000170 AC: 246 AN: 1450326 Hom.: 0 Cov.: 32 AF XY: 0.000174 AC XY: 125 AN XY: 720372

African (AFR) AF: 0.00 AC: 0 AN: 33182

American (AMR) AF: 0.00 AC: 0 AN: 43032

Ashkenazi Jewish (ASJ) AF: 0.0000387 AC: 1 AN: 25812

East Asian (EAS) AF: 0.00453 AC: 177 AN: 39096

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 84162

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52536

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.0000235 AC: 26 AN: 1106776

Other (OTH) AF: 0.000667 AC: 40 AN: 59982

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152244 Hom.: 0 Cov.: 31 AF XY: 0.000121 AC XY: 9 AN XY: 74424

African (AFR) AF: 0.00 AC: 0 AN: 41560

American (AMR) AF: 0.000131 AC: 2 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00232 AC: 12 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68006

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.0000447 Hom.: 0

Bravo AF: 0.000125

ExAC AF: 0.000174 AC: 21

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		3.2
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.044
Sift	Benign	0.25	T
Sift4G	Benign	0.30	T
Polyphen		0.0010	B
Vest4		0.25
MVP		0.45
MPC		0.45
ClinPred		0.048	T
GERP RS		2.5
Varity_R		0.016
gMVP		0.27
Mutation Taster		=90/10	polymorphism

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: rs181655124; hg19: chr17-45776016;