4-106316238-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004757.4(AIMP1):c.-132C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 282,224 control chromosomes in the GnomAD database, including 3,920 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1909 hom., cov: 31)
  • Exomes 𝑓: 0.16 (2011 hom.)
• Consequence: AIMP1 NM_004757.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.919

Genes affected

AIMP1 (HGNC:10648): (aminoacyl tRNA synthetase complex interacting multifunctional protein 1) The protein encoded by this gene is a cytokine that is specifically induced by apoptosis, and it is involved in the control of angiogenesis, inflammation, and wound healing. The release of this cytokine renders the tumor-associated vasculature sensitive to tumor necrosis factor. The precursor protein is identical to the p43 subunit, which is associated with the multi-tRNA synthetase complex, and it modulates aminoacylation activity of tRNA synthetase in normal cells. This protein is also involved in the stimulation of inflammatory responses after proteolytic cleavage in tumor cells. Multiple transcript variants encoding different isoforms have been found for this gene. A pseudogene has been identified on chromosome 20. [provided by RefSeq, Dec 2008]

TBCK (HGNC:28261): (TBC1 domain containing kinase) This gene encodes a protein that contains a protein kinase domain, a Rhodanase-like domain and the Tre-2/Bub2/Cdc16 (TBC) domain. The encoded protein is thought to play a role in actin organization, cell growth and cell proliferation by regulating the mammalian target of the rapamycin (mTOR) signaling pathway. This protein may also be involved in the transcriptional regulation of the components of the mTOR complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 4-106316238-C-T is Benign according to our data. Variant chr4-106316238-C-T is described in ClinVar as [Benign]. Clinvar id is 1272300.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TBCK	NM_001163435.3			upstream_gene_variant		ENST00000394708.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TBCK	ENST00000394708.7			upstream_gene_variant		1	NM_001163435.3	P1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23441 AN: 151880 Hom.: 1909 Cov.: 31

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.142

GnomAD4 exome AF: 0.163 AC: 21185 AN: 130226 Hom.: 2011 Cov.: 0 AF XY: 0.165 AC XY: 11129 AN XY: 67598

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.115

Gnomad4 EAS exome AF: 0.174

Gnomad4 SAS exome AF: 0.219

Gnomad4 FIN exome AF: 0.193

Gnomad4 NFE exome AF: 0.163

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.154 AC: 23451 AN: 151998 Hom.: 1909 Cov.: 31 AF XY: 0.156 AC XY: 11557 AN XY: 74254

Gnomad4 AFR AF: 0.116

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.142

Alfa AF: 0.162 Hom.: 2027

Bravo AF: 0.145

Asia WGS AF: 0.212 AC: 735 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	13
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs6814166; hg19: chr4-107237395;