rs6814166

Variant names:

• chr4-106316238-C-A
• rs6814166
• ENST00000885939.1:c.-349G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-106316238-C-A
• chr4-106316238-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004757.4(AIMP1):​c.-132C>A variant causes a 5 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AIMP1 NM_004757.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.919
• Publications: 10 publications found

Genes affected

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]

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]

AIMP1 Gene-Disease associations (from GenCC):

• hypomyelinating leukodystrophy 3

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), G2P
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004757.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIMP1	NM_004757.4		c.-132C>A		5_prime_UTR	Exon 1 of 7	NP_004748.2
	TBCK	NM_001163436.4		c.-30+310G>T		intron	N/A	NP_001156908.2	Q8TEA7-1
	AIMP1	NM_001142415.2		c.-26+602C>A		intron	N/A	NP_001135887.1	Q12904-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TBCK	ENST00000885939.1		c.-349G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 26	ENSP00000555998.1
	TBCK	ENST00000509532.5	TSL:5	c.-341G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000420985.1	D6RDG2
	TBCK	ENST00000885939.1		c.-349G>T		5_prime_UTR	Exon 1 of 26	ENSP00000555998.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 130552 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 67758

African (AFR) AF: 0.00 AC: 0 AN: 4474

American (AMR) AF: 0.00 AC: 0 AN: 4894

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4720

East Asian (EAS) AF: 0.00 AC: 0 AN: 9404

South Asian (SAS) AF: 0.00 AC: 0 AN: 8832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 716

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 80564

Other (OTH) AF: 0.00 AC: 0 AN: 8350

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	12
DANN	Benign	0.74
PhyloP100		0.92
PromoterAI		-0.45	Neutral

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

Other links and lift over

dbSNP: rs6814166; hg19: chr4-107237395;