rs199641620

Variant names:

• chr2-161231000-A-G
• NM_001199135.3:c.550A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-161231000-A-G
• chr2-161231000-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1 PM2 BS2

The NM_001199135.3(TANK):​c.550A>G​(p.Thr184Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: TANK NM_001199135.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.34

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.

• PM1: In a mutagenesis_site Abolishes interaction with TRAF2 and TRAF3. (size 0) in uniprot entity TANK_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TANK	NM_001199135.3	c.550A>G	p.Thr184Ala	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.550A>G	p.Thr184Ala	missense_variant	Exon 7 of 8	1	NM_001199135.3	ENSP00000376505.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461826 Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5 AN XY: 727214

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: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T;T;T;T;T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	.;T;D;D;D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.47	T;T;T;T;T
MetaSVM	Benign	-0.40	T
MutationAssessor	Uncertain	2.4	M;M;.;.;.
PrimateAI	Uncertain	0.48	T
PROVEAN	Uncertain	-2.7	D;D;D;D;D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0050	D;D;D;D;D
Sift4G	Uncertain	0.010	D;D;D;D;D
Polyphen		1.0	D;D;.;.;.
Vest4		0.85
MutPred		0.34		Loss of methylation at K189 (P = 0.0838);Loss of methylation at K189 (P = 0.0838);.;Loss of methylation at K189 (P = 0.0838);.;
MVP		0.64
MPC		0.98
ClinPred		0.94	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.74
gMVP		0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-162087511;