NM_006303.4:c.48C>G

Variant names:

• chr7-6009411-C-G
• NM_006303.4:c.48C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_006303.4(AIMP2):​c.48C>G​(p.Leu16Leu) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AIMP2 NM_006303.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.74
• Publications: 0 publications found

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]

AIMP2 Gene-Disease associations (from GenCC):

• leukodystrophy, hypomyelinating, 17

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Illumina, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 7-6009411-C-G is Benign according to our data. Variant chr7-6009411-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3650022.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.74 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AIMP2	NM_006303.4	c.48C>G	p.Leu16Leu	synonymous_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.48C>G	p.Leu16Leu	synonymous_variant	Exon 1 of 4	1	NM_006303.4	ENSP00000223029.3
AIMP2	ENST00000395236.2	c.48C>G	p.Leu16Leu	synonymous_variant	Exon 1 of 3	2		ENSP00000378658.2
AIMP2	ENST00000415999.1	n.48C>G		non_coding_transcript_exon_variant	Exon 1 of 3	3		ENSP00000392519.1
AIMP2	ENST00000400479.6	c.-251+33C>G		intron_variant	Intron 1 of 4	5		ENSP00000383327.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 25, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	13
DANN	Benign	0.83
PhyloP100		1.7
PromoterAI		-0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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

Other links and lift over

hg19: chr7-6049042;