4-106325080-A-G

Variant names:

• chr4-106325080-A-G
• rs369840696
• NM_001142416.2:c.71A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001142416.2(AIMP1):​c.71A>G​(p.Tyr24Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,810 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: AIMP1 NM_001142416.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.43

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AIMP1	NM_001142416.2	c.71A>G	p.Tyr24Cys	missense_variant	Exon 2 of 7	ENST00000672341.1	NP_001135888.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AIMP1	ENST00000672341.1	c.71A>G	p.Tyr24Cys	missense_variant	Exon 2 of 7		NM_001142416.2	ENSP00000500620.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460810 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726732

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.059	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;T;T;.
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D;D;.;D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.48	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Pathogenic	3.0	.;M;M;.
PrimateAI	Pathogenic	0.80	D
PROVEAN	Uncertain	-4.0	D;D;D;D
REVEL	Benign	0.27
Sift	Uncertain	0.0030	D;T;T;T
Sift4G	Uncertain	0.0080	D;T;T;T
Polyphen		1.0	.;D;D;.
Vest4		0.76, 0.77
MutPred		0.42		Gain of catalytic residue at L25 (P = 0.0223);Gain of catalytic residue at L25 (P = 0.0223);Gain of catalytic residue at L25 (P = 0.0223);.;
MVP		0.44
MPC		0.22
ClinPred		0.99	D
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.61
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs369840696; hg19: chr4-107246237;