Genetic Variant AIMP2:p.Pro37Thr (chr7-6009472-C-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006303.4(AIMP2):c.109C>A(p.Pro37Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000184 in 1,589,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. P37A) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

AIMP2
NM_006303.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.117

Publications

4 publications found

Variant links:

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)

AIMP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05682212).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AIMP2	NM_006303.4	MANE Select	c.109C>A	p.Pro37Thr	missense	Exon 1 of 4	NP_006294.2
AIMP2	NM_001326607.2		c.109C>A	p.Pro37Thr	missense	Exon 1 of 3	NP_001313536.1
AIMP2	NM_001326609.2		c.-212C>A		5_prime_UTR	Exon 1 of 5	NP_001313538.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AIMP2	ENST00000223029.8	TSL:1 MANE Select	c.109C>A	p.Pro37Thr	missense	Exon 1 of 4	ENSP00000223029.3
AIMP2	ENST00000395236.2	TSL:2	c.109C>A	p.Pro37Thr	missense	Exon 1 of 3	ENSP00000378658.2
AIMP2	ENST00000415999.1	TSL:3	n.109C>A		non_coding_transcript_exon	Exon 1 of 3	ENSP00000392519.1

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000527

AC:

AN:

227908

AF XY:

0.0000478

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000191

AC:

274

AN:

1437596

Hom.:

Cov.:

AF XY:

0.000185

AC XY:

132

AN XY:

714642

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31820

American (AMR)

AF:

0.00

AC:

AN:

39450

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25062

East Asian (EAS)

AF:

0.00

AC:

AN:

38156

South Asian (SAS)

AF:

0.00

AC:

AN:

84476

European-Finnish (FIN)

AF:

0.0000192

AC:

AN:

52046

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4056

European-Non Finnish (NFE)

AF:

0.000240

AC:

265

AN:

1103468

Other (OTH)

AF:

0.000135

AC:

AN:

59062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000118

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41444

American (AMR)

AF:

0.0000655

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

67984

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000220

Hom.:

ExAC

AF:

0.0000496

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.1

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.021

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.59

M_CAP

Benign

0.015

MetaRNN

Benign

0.057

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.6

PhyloP100

0.12

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.060

REVEL

Benign

0.027

Sift

Benign

0.63

Sift4G

Benign

0.76

Polyphen

0.0

Vest4

0.32

MutPred

0.15

Gain of phosphorylation at P37 (P = 0.0789)

MVP

0.048

MPC

0.033

ClinPred

0.041

GERP RS

1.0

PromoterAI

-0.024

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.035

gMVP

0.26

Mutation Taster

=93/7

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over