17-47696314-C-G

Variant names:

• chr17-47696314-C-G
• rs367892556
• NM_001394755.1:c.202C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001394755.1(TBKBP1):​c.202C>G​(p.Arg68Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,036 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R68C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: TBKBP1 NM_001394755.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.09

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34473088).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TBKBP1	NM_001394755.1	c.202C>G	p.Arg68Gly	missense_variant	Exon 2 of 10	ENST00000578982.6	NP_001381684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TBKBP1	ENST00000578982.6	c.202C>G	p.Arg68Gly	missense_variant	Exon 2 of 10	3	NM_001394755.1	ENSP00000462339.2
TBKBP1	ENST00000361722.7	c.202C>G	p.Arg68Gly	missense_variant	Exon 1 of 9	1		ENSP00000354777.3
TBKBP1	ENST00000537587.6	c.202C>G	p.Arg68Gly	missense_variant	Exon 2 of 5	3		ENSP00000446365.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152108 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000821 AC: 12 AN: 1460928 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 726738

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152108 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74292

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.20	T;.;T;.
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.85	T;T;T;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.34	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	.;.;M;M
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-6.0	.;D;D;.
REVEL	Benign	0.20
Sift	Uncertain	0.0010	.;D;D;.
Sift4G	Uncertain	0.0070	D;D;D;D
Polyphen		0.93	.;.;P;.
Vest4		0.57, 0.68
MutPred		0.39		Loss of stability (P = 0.002);Loss of stability (P = 0.002);Loss of stability (P = 0.002);Loss of stability (P = 0.002);
MVP		0.35
MPC		1.1
ClinPred		0.98	D
GERP RS		4.0
Varity_R		0.60
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

LitVar

Other links and lift over

dbSNP: rs367892556; hg19: chr17-45773680;