rs1289756357

Variant names:

• chr7-6009449-A-C
• rs1289756357
• NM_006303.4:c.86A>C

Your query was ambiguous. Multiple possible variants found:

• chr7-6009449-A-C
• chr7-6009449-A-G
• chr7-6009449-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006303.4(AIMP2):​c.86A>C​(p.Asn29Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,284 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. N29K) 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: 2.08
• 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), ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006303.4. 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
	AIMP2	NM_006303.4	MANE Select	c.86A>C	p.Asn29Thr	missense	Exon 1 of 4	NP_006294.2
	AIMP2	NM_001326607.2		c.86A>C	p.Asn29Thr	missense	Exon 1 of 3	NP_001313536.1	Q13155-2
	AIMP2	NM_001326609.2		c.-235A>C		5_prime_UTR	Exon 1 of 5	NP_001313538.1	A8MU58

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIMP2	ENST00000223029.8	TSL:1 MANE Select	c.86A>C	p.Asn29Thr	missense	Exon 1 of 4	ENSP00000223029.3	Q13155-1
	AIMP2	ENST00000395236.2	TSL:2	c.86A>C	p.Asn29Thr	missense	Exon 1 of 3	ENSP00000378658.2	Q13155-2
	AIMP2	ENST00000400479.6	TSL:5	c.-251+71A>C		intron	N/A	ENSP00000383327.2	A8MU58

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458284 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 725432

African (AFR) AF: 0.00 AC: 0 AN: 33382

American (AMR) AF: 0.00 AC: 0 AN: 44558

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39632

South Asian (SAS) AF: 0.00 AC: 0 AN: 86098

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52538

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4152

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111662

Other (OTH) AF: 0.00 AC: 0 AN: 60172

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.058	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.54	D
Eigen	Benign	0.15
Eigen_PC	Benign	0.12
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.1
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.17
Sift	Benign	0.065	T
Sift4G	Benign	0.64	T
Polyphen		0.86	P
Vest4		0.56
MutPred		0.57		Gain of glycosylation at N29 (P = 0.0158)
MVP		0.31
MPC		0.060
ClinPred		0.89	D
GERP RS		2.7
PromoterAI		0.045	Neutral
Varity_R		0.31
gMVP		0.43
Mutation Taster		=79/21	polymorphism

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: rs1289756357; hg19: chr7-6049080;