rs113844295

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001142416.2(AIMP1):c.310A>G(p.Thr104Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00188 in 1,613,570 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T104T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0097 ( 21 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 36 hom. )

Consequence

AIMP1
NM_001142416.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.564

Publications

5 publications found

Variant links:

Genes affected

AIMP1 (HGNC:10648): (aminoacyl tRNA synthetase complex interacting multifunctional protein 1) The protein encoded by this gene is a cytokine that is specifically induced by apoptosis, and it is involved in the control of angiogenesis, inflammation, and wound healing. The release of this cytokine renders the tumor-associated vasculature sensitive to tumor necrosis factor. The precursor protein is identical to the p43 subunit, which is associated with the multi-tRNA synthetase complex, and it modulates aminoacylation activity of tRNA synthetase in normal cells. This protein is also involved in the stimulation of inflammatory responses after proteolytic cleavage in tumor cells. Multiple transcript variants encoding different isoforms have been found for this gene. A pseudogene has been identified on chromosome 20. [provided by RefSeq, Dec 2008]

AIMP1 Gene-Disease associations (from GenCC):

hypomyelinating leukodystrophy 3
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Orphanet
autosomal recessive non-syndromic intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

AIMP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0024947822).

BP6

Variant 4-106328162-A-G is Benign according to our data. Variant chr4-106328162-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 446035.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00974 (1483/152316) while in subpopulation AFR AF = 0.034 (1415/41562). AF 95% confidence interval is 0.0326. There are 21 homozygotes in GnomAd4. There are 706 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AIMP1	NM_001142416.2 link	c.310A>G	p.Thr104Ala	missense_variant	Exon 4 of 7	ENST00000672341.1	NP_001135888.2	Q12904-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AIMP1	ENST00000672341.1 link	c.310A>G	p.Thr104Ala	missense_variant	Exon 4 of 7		NM_001142416.2	ENSP00000500620.1		Q12904-1

Frequencies

GnomAD3 genomes

AF:

0.00973

AC:

1481

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0341

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000413

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00672

GnomAD2 exomes

AF:

0.00249

AC:

625

AN:

251090

AF XY:

0.00178

show subpopulations

Gnomad AFR exome

AF:

0.0347

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00106

AC:

1549

AN:

1461254

Hom.:

Cov.:

AF XY:

0.000907

AC XY:

659

AN XY:

726912

show subpopulations

African (AFR)

AF:

0.0376

AC:

1256

AN:

33438

American (AMR)

AF:

0.00152

AC:

AN:

44652

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39624

South Asian (SAS)

AF:

0.000128

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53362

Middle Eastern (MID)

AF:

0.00278

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000351

AC:

AN:

1111680

Other (OTH)

AF:

0.00263

AC:

159

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

149

223

298

372

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<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:

0.00974

AC:

1483

AN:

152316

Hom.:

Cov.:

AF XY:

0.00948

AC XY:

706

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.0340

AC:

1415

AN:

41562

American (AMR)

AF:

0.00261

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000414

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68016

Other (OTH)

AF:

0.00665

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

141

211

282

352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00662

Hom.:

Bravo

AF:

0.0109

ESP6500AA

AF:

0.0325

AC:

143

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00320

AC:

388

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Apr 24, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 15, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.032

(source)

DANN

Benign

0.26

DEOGEN2

Benign

0.0088

T;T;T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.27

T;T;.;T

MetaRNN

Benign

0.0025

T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.020

.;N;N;.

PhyloP100

-0.56

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.25

N;N;N;N

REVEL

Benign

0.022

Sift

Benign

0.38

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

.;B;B;.

Vest4

0.055, 0.056, 0.049

MVP

0.040

MPC

0.025

ClinPred

0.00048

GERP RS

-3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.017

gMVP

0.13

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over