7-6016853-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006303.4(AIMP2):c.343-961G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 153,332 control chromosomes in the GnomAD database, including 3,829 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (3807 hom., cov: 32)
  • Exomes 𝑓: 0.19 (22 hom.)
• Consequence: AIMP2 NM_006303.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930

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]

SNORA80D (HGNC:50435): (small nucleolar RNA, H/ACA box 80D)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AIMP2	NM_006303.4	c.343-961G>C		intron_variant		ENST00000223029.8
SNORA80D	NR_145771.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AIMP2	ENST00000223029.8	c.343-961G>C		intron_variant		1	NM_006303.4	P1
AIMP2	ENST00000395236.2	c.136-961G>C		intron_variant		2
AIMP2	ENST00000400479.6	c.109-961G>C		intron_variant		5
SNORA80D	ENST00000384488.1			upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32562 AN: 151948 Hom.: 3805 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.207

GnomAD4 exome AF: 0.194 AC: 245 AN: 1264 Hom.: 22 Cov.: 0 AF XY: 0.204 AC XY: 131 AN XY: 642

Gnomad4 AFR exome AF: 0.289

Gnomad4 AMR exome AF: 0.167

Gnomad4 EAS exome AF: 0.538

Gnomad4 SAS exome AF: 0.156

Gnomad4 FIN exome AF: 0.292

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.198

GnomAD4 genome AF: 0.214 AC: 32574 AN: 152068 Hom.: 3807 Cov.: 32 AF XY: 0.220 AC XY: 16358 AN XY: 74332

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.210

Alfa AF: 0.107 Hom.: 169

Bravo AF: 0.207

Asia WGS AF: 0.360 AC: 1250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	4.7
Dann	Benign	0.77

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: rs3779109; hg19: chr7-6056484; COSMIC: COSV56152065; COSMIC: COSV56152065;