NM_001142416.2:c.10_12delAAT

Variant names:

• chr4-106325015-AAAT-A
• rs769350799
• NM_001142416.2:c.10_12delAAT

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PM4_Supporting

The NM_001142416.2(AIMP1):​c.10_12delAAT​(p.Asn4del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,603,180 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: AIMP1 NM_001142416.2 conservative_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2 O:1
• Conservation: PhyloP100: 2.61
• Publications: 0 publications found

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]

AIMP1 Gene-Disease associations (from GenCC):

• hypomyelinating leukodystrophy 3

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001142416.2. Strenght limited to Supporting due to length of the change: 1aa.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142416.2. 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_001142416.2	MANE Select	c.10_12delAAT	p.Asn4del	conservative_inframe_deletion	Exon 2 of 7	NP_001135888.2	Q12904-1
	AIMP1	NM_001142415.2		c.10_12delAAT	p.Asn4del	conservative_inframe_deletion	Exon 2 of 7	NP_001135887.1	Q12904-1
	AIMP1	NM_004757.4		c.10_12delAAT	p.Asn4del	conservative_inframe_deletion	Exon 2 of 7	NP_004748.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIMP1	ENST00000672341.1	MANE Select	c.10_12delAAT	p.Asn4del	conservative_inframe_deletion	Exon 2 of 7	ENSP00000500620.1	Q12904-1
	AIMP1	ENST00000394701.6	TSL:1	c.-161-2432_-161-2430delAAT		intron	N/A	ENSP00000378191.5	A0A8C8KIA0
	AIMP1	ENST00000358008.7	TSL:2	c.10_12delAAT	p.Asn4del	conservative_inframe_deletion	Exon 2 of 7	ENSP00000350699.3	Q12904-1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152108 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000408 AC: 10 AN: 245392 AF XY: 0.0000377

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000181

Gnomad ASJ exome AF: 0.000304

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000207 AC: 30 AN: 1451072 Hom.: 0 AF XY: 0.0000194 AC XY: 14 AN XY: 721260

African (AFR) AF: 0.00 AC: 0 AN: 33132

American (AMR) AF: 0.000229 AC: 10 AN: 43644

Ashkenazi Jewish (ASJ) AF: 0.000194 AC: 5 AN: 25800

East Asian (EAS) AF: 0.00 AC: 0 AN: 39446

South Asian (SAS) AF: 0.0000241 AC: 2 AN: 83042

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53142

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5646

European-Non Finnish (NFE) AF: 0.00000722 AC: 8 AN: 1107272

Other (OTH) AF: 0.0000834 AC: 5 AN: 59948

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152108 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74312

African (AFR) AF: 0.0000241 AC: 1 AN: 41446

American (AMR) AF: 0.0000655 AC: 1 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67950

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	not provided (2)
-	-	-	Hypomyelinating leukodystrophy 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs769350799; hg19: chr4-107246172;