Variant chr7-6009464-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006303.4(AIMP2):c.101G>A(p.Ser34Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

AIMP2
NM_006303.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0900

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.059502274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AIMP2	NM_006303.4 linkuse as main transcript	c.101G>A	p.Ser34Asn	missense_variant	1/4	ENST00000223029.8	NP_006294.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AIMP2	ENST00000223029.8 linkuse as main transcript	c.101G>A	p.Ser34Asn	missense_variant	1/4	1	NM_006303.4	ENSP00000223029	P1	Q13155-1
AIMP2	ENST00000395236.2 linkuse as main transcript	c.101G>A	p.Ser34Asn	missense_variant	1/3	2		ENSP00000378658		Q13155-2
AIMP2	ENST00000400479.6 linkuse as main transcript	c.-251+86G>A		intron_variant		5		ENSP00000383327
AIMP2	ENST00000415999.1 linkuse as main transcript	c.101G>A	p.Ser34Asn	missense_variant, NMD_transcript_variant	1/3	3		ENSP00000392519

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455850

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724268

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 20, 2021

The c.101G>A (p.S34N) alteration is located in exon 1 (coding exon 1) of the AIMP2 gene. This alteration results from a G to A substitution at nucleotide position 101, causing the serine (S) at amino acid position 34 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.6

DANN

Benign

0.86

DEOGEN2

Benign

0.042

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.51

T;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.060

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.70

N;N

REVEL

Benign

0.022

Sift

Benign

0.18

T;D

Sift4G

Benign

0.22

T;T

Polyphen

0.0

B;.

Vest4

0.10

MutPred

0.16

Loss of phosphorylation at S34 (P = 0.0521);Loss of phosphorylation at S34 (P = 0.0521);

MVP

0.030

MPC

0.030

ClinPred

0.12

GERP RS

-3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.058

gMVP

0.12

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over