rs374542185

Variant names:

• chr2-161231121-C-G
• NM_001199135.3:c.671C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-161231121-C-G
• chr2-161231121-C-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.671C>G​(p.Thr224Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TANK NM_001199135.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.782

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=0.09273428).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TANK	NM_001199135.3	c.671C>G	p.Thr224Ser	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.671C>G	p.Thr224Ser	missense_variant	Exon 7 of 8	1	NM_001199135.3	ENSP00000376505.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461828 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727210

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T;T;T;T
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.0080
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.63	.;T;T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.093	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L;.;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.70	N;N;N;N
REVEL	Benign	0.022
Sift	Benign	0.40	T;T;T;T
Sift4G	Benign	0.62	T;T;T;T
Polyphen		0.45	B;B;.;.
Vest4		0.17
MutPred		0.12		Gain of phosphorylation at T224 (P = 0.0532);Gain of phosphorylation at T224 (P = 0.0532);Gain of phosphorylation at T224 (P = 0.0532);.;
MVP		0.41
MPC		0.28
ClinPred		0.19	T
GERP RS		2.6
Varity_R		0.039
gMVP		0.067

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: chr2-162087632;