chr7-6009472-C-T

Position:

• chr7-6009472-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: AIMP2 NM_006303.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117

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]

ACMG classification

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=0.050261706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AIMP2	NM_006303.4	c.109C>T	p.Pro37Ser	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	c.109C>T	p.Pro37Ser	missense_variant	1/4	1	NM_006303.4	ENSP00000223029.3
AIMP2	ENST00000395236.2	c.109C>T	p.Pro37Ser	missense_variant	1/3	2		ENSP00000378658.2
AIMP2	ENST00000400479.6	c.-251+94C>T		intron_variant		5		ENSP00000383327.2
AIMP2	ENST00000415999.1	n.109C>T		non_coding_transcript_exon_variant	1/3	3		ENSP00000392519.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1437600 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 714644

Gnomad4 AFR exome AF: 0.0000629

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.0
DANN	Benign	0.79
DEOGEN2	Benign	0.016	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.52	T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.050	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.61	N;N
REVEL	Benign	0.025
Sift	Benign	0.64	T;T
Sift4G	Benign	0.73	T;T
Polyphen		0.0	B;.
Vest4		0.11
MutPred		0.11		Gain of phosphorylation at P37 (P = 0.0584);Gain of phosphorylation at P37 (P = 0.0584);
MVP		0.048
MPC		0.032
ClinPred		0.041	T
GERP RS		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.021
gMVP		0.22

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

LitVar

Other links and lift over

dbSNP: rs6977072; hg19: chr7-6049103;