Genetic Variant AIMP2:p.Pro37Ser (chr7-6009472-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006303.4(AIMP2):c.109C>T(p.Pro37Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,437,600 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.050261706).

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>T	p.Pro37Ser	missense	Exon 1 of 4	NP_006294.2
AIMP2	NM_001326607.2		c.109C>T	p.Pro37Ser	missense	Exon 1 of 3	NP_001313536.1
AIMP2	NM_001326609.2		c.-212C>T		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>T	p.Pro37Ser	missense	Exon 1 of 4	ENSP00000223029.3
AIMP2	ENST00000395236.2	TSL:2	c.109C>T	p.Pro37Ser	missense	Exon 1 of 3	ENSP00000378658.2
AIMP2	ENST00000415999.1	TSL:3	n.109C>T		non_coding_transcript_exon	Exon 1 of 3	ENSP00000392519.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

227908

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1437600

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

714644

show subpopulations

African (AFR)

AF:

0.0000629

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:

84478

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52046

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4056

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1103470

Other (OTH)

AF:

0.00

AC:

AN:

59062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.0

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.016

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.52

M_CAP

Benign

0.021

MetaRNN

Benign

0.050

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.2

PhyloP100

0.12

PrimateAI

Benign

0.42

PROVEAN

Benign

0.61

REVEL

Benign

0.025

Sift

Benign

0.64

Sift4G

Benign

0.73

Polyphen

0.0

Vest4

0.11

MutPred

0.11

Gain of phosphorylation at P37 (P = 0.0584)

MVP

0.048

MPC

0.032

ClinPred

0.041

GERP RS

1.0

PromoterAI

-0.075

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.021

gMVP

0.22

Mutation Taster

=96/4

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over