rs768787708

Variant names:

• chr7-6009409-C-A
• rs768787708
• NM_006303.4:c.46C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-6009409-C-A
• chr7-6009409-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006303.4(AIMP2):​c.46C>A​(p.Leu16Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L16F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: AIMP2 NM_006303.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45

Genes affected

AIMP2 (HGNC:20609): (aminoacyl tRNA synthetase complex interacting multifunctional protein 2) The protein encoded by this gene is part of the aminoacyl-tRNA synthetase complex, which contains nine different aminoacyl-tRNA synthetases and three non-enzymatic factors. The encoded protein is one of the non-enzymatic factors and is required for assembly and stability of the complex. [provided by RefSeq, May 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09096953).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AIMP2	NM_006303.4	c.46C>A	p.Leu16Ile	missense_variant	Exon 1 of 4	ENST00000223029.8	NP_006294.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AIMP2	ENST00000223029.8	c.46C>A	p.Leu16Ile	missense_variant	Exon 1 of 4	1	NM_006303.4	ENSP00000223029.3
AIMP2	ENST00000395236.2	c.46C>A	p.Leu16Ile	missense_variant	Exon 1 of 3	2		ENSP00000378658.2
AIMP2	ENST00000400479.6	c.-251+31C>A		intron_variant	Intron 1 of 4	5		ENSP00000383327.2
AIMP2	ENST00000415999.1	n.46C>A		non_coding_transcript_exon_variant	Exon 1 of 3	3		ENSP00000392519.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459304 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 725960

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T;.
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.091	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.33	N;N
REVEL	Benign	0.036
Sift	Benign	1.0	T;D
Sift4G	Benign	1.0	T;T
Polyphen		0.018	B;.
Vest4		0.16
MutPred		0.26		Loss of catalytic residue at L16 (P = 0.0503);Loss of catalytic residue at L16 (P = 0.0503);
MVP		0.076
MPC		0.036
ClinPred		0.20	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.20
gMVP		0.22

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

Publications

LitVar

Other links and lift over

dbSNP: rs768787708; hg19: chr7-6049040;