2-161231364-C-T

Variant names:

• chr2-161231364-C-T
• rs149311409
• NM_001199135.3:c.914C>T

Variant summary

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

The NM_001199135.3(TANK):​c.914C>T​(p.Thr305Ile) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TANK NM_001199135.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.84

Genes affected

TANK (HGNC:11562): (TRAF family member associated NFKB activator) The TRAF (tumor necrosis factor receptor-associated factor) family of proteins associate with and transduce signals from members of the tumor necrosis factor receptor superfamily. The protein encoded by this gene is found in the cytoplasm and can bind to TRAF1, TRAF2, or TRAF3, thereby inhibiting TRAF function by sequestering the TRAFs in a latent state in the cytoplasm. For example, the protein encoded by this gene can block TRAF2 binding to LMP1, the Epstein-Barr virus transforming protein, and inhibit LMP1-mediated NF-kappa-B activation. Three alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

PSMD14-DT (HGNC:56104): (PSMD14 divergent transcript)

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=0.13149726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TANK	NM_001199135.3	c.914C>T	p.Thr305Ile	missense_variant	Exon 7 of 8	ENST00000392749.7	NP_001186064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TANK	ENST00000392749.7	c.914C>T	p.Thr305Ile	missense_variant	Exon 7 of 8	1	NM_001199135.3	ENSP00000376505.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	19
DANN	Benign	0.89
DEOGEN2	Benign	0.30	T;T;T;T;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.018
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.78	.;T;T;T;T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.13	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L;.;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.7	N;N;N;N;D
REVEL	Benign	0.025
Sift	Benign	0.34	T;T;T;T;T
Sift4G	Benign	0.55	T;T;T;T;T
Polyphen		0.0070	B;B;.;.;.
Vest4		0.13
MutPred		0.36		Loss of ubiquitination at K304 (P = 0.0298);Loss of ubiquitination at K304 (P = 0.0298);Loss of ubiquitination at K304 (P = 0.0298);.;.;
MVP		0.18
MPC		0.33
ClinPred		0.26	T
GERP RS		4.7
Varity_R		0.057
gMVP		0.34

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: rs149311409; hg19: chr2-162087875;