Variant 2-161204726-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001199135.3(TANK):c.260A>G(p.Asn87Ser) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

TANK
NM_001199135.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.71

Variant links:

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]

TANK links:

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ACMG classification

Classification made for transcript

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=0.13071084).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TANK	NM_001199135.3 linkuse as main transcript	c.260A>G	p.Asn87Ser	missense_variant	4/8	ENST00000392749.7	NP_001186064.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TANK	ENST00000392749.7 linkuse as main transcript	c.260A>G	p.Asn87Ser	missense_variant	4/8	1	NM_001199135.3	ENSP00000376505	P1	Q92844-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

The c.260A>G (p.N87S) alteration is located in exon 4 (coding exon 3) of the TANK gene. This alteration results from a A to G substitution at nucleotide position 260, causing the asparagine (N) at amino acid position 87 to be replaced by a serine (S). 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

0.11

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.099

T;T;T;T;T;T;.;T;.;.

Eigen

Benign

0.11

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.86

.;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.0066

MetaRNN

Benign

0.13

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;.;M;.;.;.;.;.;.;M

MutationTaster

Benign

0.98

N;N;N;N;N;N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.0

N;D;N;D;N;N;N;N;D;D

REVEL

Benign

0.046

Sift

Benign

0.19

T;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.54

T;T;T;T;T;T;T;T;T;T

Polyphen

0.93

P;.;P;.;.;.;.;.;.;.

Vest4

0.41

MutPred

0.20

Loss of loop (P = 9e-04);.;Loss of loop (P = 9e-04);Loss of loop (P = 9e-04);.;.;.;Loss of loop (P = 9e-04);.;Loss of loop (P = 9e-04);

MVP

0.24

MPC

0.37

ClinPred

0.52

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.051

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over