chr2-161231523-C-T

Position:

• chr2-161231523-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001199135.3(TANK):​c.1073C>T​(p.Pro358Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00337 in 1,612,588 control chromosomes in the GnomAD database, including 143 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.016 (62 hom., cov: 33)
  • Exomes 𝑓: 0.0020 (81 hom.)
• Consequence: TANK NM_001199135.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.99

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003142953).
• BP6: Variant 2-161231523-C-T is Benign according to our data. Variant chr2-161231523-C-T is described in ClinVar as [Benign]. Clinvar id is 775768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TANK	NM_001199135.3	c.1073C>T	p.Pro358Leu	missense_variant	7/8	ENST00000392749.7
PSMD14-DT	NR_110593.1	n.349-8040G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TANK	ENST00000392749.7	c.1073C>T	p.Pro358Leu	missense_variant	7/8	1	NM_001199135.3	P1

Frequencies

GnomAD3 genomes AF: 0.0163 AC: 2475 AN: 152064 Hom.: 61 Cov.: 33

Gnomad AFR AF: 0.0555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00648

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0162

GnomAD3 exomes AF: 0.00462 AC: 1148 AN: 248646 Hom.: 24 AF XY: 0.00340 AC XY: 458 AN XY: 134788

Gnomad AFR exome AF: 0.0578

Gnomad AMR exome AF: 0.00356

Gnomad ASJ exome AF: 0.00318

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000354

Gnomad OTH exome AF: 0.00327

GnomAD4 exome AF: 0.00202 AC: 2953 AN: 1460406 Hom.: 81 Cov.: 32 AF XY: 0.00181 AC XY: 1313 AN XY: 726608

Gnomad4 AFR exome AF: 0.0632

Gnomad4 AMR exome AF: 0.00402

Gnomad4 ASJ exome AF: 0.00287

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000336

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000181

Gnomad4 OTH exome AF: 0.00523

GnomAD4 genome AF: 0.0163 AC: 2479 AN: 152182 Hom.: 62 Cov.: 33 AF XY: 0.0159 AC XY: 1180 AN XY: 74406

Gnomad4 AFR AF: 0.0555

Gnomad4 AMR AF: 0.00641

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.00208 Hom.: 14

Bravo AF: 0.0189

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0522 AC: 230

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00548 AC: 665

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T;T;T;T;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.93	.;D;D;D;D
MetaRNN	Benign	0.0031	T;T;T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.4	M;M;.;.;.
MutationTaster	Benign	0.99	D;D;D;D;D
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-3.7	D;D;D;D;D
REVEL	Benign	0.15
Sift	Uncertain	0.0030	D;D;D;D;D
Sift4G	Uncertain	0.011	D;D;D;D;D
Polyphen		0.99	D;D;.;.;.
Vest4		0.16
MVP		0.27
MPC		0.88
ClinPred		0.031	T
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.44

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

LitVar

Other links and lift over

dbSNP: rs2229759; hg19: chr2-162088034;