NM_006303.4:c.924C>T

Variant names:

• chr7-6023652-C-T
• rs4560
• NM_006303.4:c.924C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_006303.4(AIMP2):​c.924C>T​(p.Asn308Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 1,613,692 control chromosomes in the GnomAD database, including 132,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (10008 hom., cov: 32)
  • Exomes 𝑓: 0.41 (122466 hom.)
• Consequence: AIMP2 NM_006303.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.36
• Publications: 42 publications found

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]

EIF2AK1 (HGNC:24921): (eukaryotic translation initiation factor 2 alpha kinase 1) The protein encoded by this gene acts at the level of translation initiation to downregulate protein synthesis in response to stress. The encoded protein is a kinase that can be inactivated by hemin. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]

EIF2AK1 Gene-Disease associations (from GenCC):

• leukoencephalopathy, motor delay, spasticity, and dysarthria syndrome

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 7-6023652-C-T is Benign according to our data. Variant chr7-6023652-C-T is described in ClinVar as Benign. ClinVar VariationId is 1166059.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.36 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIMP2	NM_006303.4	MANE Select	c.924C>T	p.Asn308Asn	synonymous	Exon 4 of 4	NP_006294.2
	EIF2AK1	NM_014413.4	MANE Select	c.*1021G>A		3_prime_UTR	Exon 15 of 15	NP_055228.2
	AIMP2	NM_001362785.2		c.837C>T	p.Asn279Asn	synonymous	Exon 5 of 5	NP_001349714.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AIMP2	ENST00000223029.8	TSL:1 MANE Select	c.924C>T	p.Asn308Asn	synonymous	Exon 4 of 4	ENSP00000223029.3	Q13155-1
	EIF2AK1	ENST00000199389.11	TSL:1 MANE Select	c.*1021G>A		3_prime_UTR	Exon 15 of 15	ENSP00000199389.6	Q9BQI3-1
	AIMP2	ENST00000395236.2	TSL:2	c.717C>T	p.Asn239Asn	synonymous	Exon 3 of 3	ENSP00000378658.2	Q13155-2

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52495 AN: 151802 Hom.: 10003 Cov.: 32

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.368

GnomAD2 exomes AF: 0.376 AC: 93532 AN: 248868 AF XY: 0.383

Gnomad AFR exome AF: 0.185

Gnomad AMR exome AF: 0.325

Gnomad ASJ exome AF: 0.440

Gnomad EAS exome AF: 0.381

Gnomad FIN exome AF: 0.343

Gnomad NFE exome AF: 0.426

Gnomad OTH exome AF: 0.392

GnomAD4 exome AF: 0.406 AC: 593549 AN: 1461772 Hom.: 122466 Cov.: 57 AF XY: 0.407 AC XY: 295764 AN XY: 727180

African (AFR) AF: 0.177 AC: 5910 AN: 33478

American (AMR) AF: 0.329 AC: 14711 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 11551 AN: 26134

East Asian (EAS) AF: 0.384 AC: 15258 AN: 39700

South Asian (SAS) AF: 0.352 AC: 30360 AN: 86238

European-Finnish (FIN) AF: 0.344 AC: 18354 AN: 53418

Middle Eastern (MID) AF: 0.466 AC: 2687 AN: 5768

European-Non Finnish (NFE) AF: 0.423 AC: 470674 AN: 1111934

Other (OTH) AF: 0.398 AC: 24044 AN: 60396

GnomAD4 genome AF: 0.346 AC: 52515 AN: 151920 Hom.: 10008 Cov.: 32 AF XY: 0.342 AC XY: 25387 AN XY: 74256

African (AFR) AF: 0.190 AC: 7876 AN: 41454

American (AMR) AF: 0.363 AC: 5537 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1517 AN: 3466

East Asian (EAS) AF: 0.384 AC: 1978 AN: 5154

South Asian (SAS) AF: 0.344 AC: 1662 AN: 4826

European-Finnish (FIN) AF: 0.348 AC: 3661 AN: 10532

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.427 AC: 29024 AN: 67920

Other (OTH) AF: 0.365 AC: 771 AN: 2114

Alfa AF: 0.399 Hom.: 38718

Bravo AF: 0.340

Asia WGS AF: 0.315 AC: 1099 AN: 3478

EpiCase AF: 0.438

EpiControl AF: 0.440

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	12
DANN	Benign	0.90
PhyloP100		2.4
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs4560; hg19: chr7-6063283; COSMIC: COSV52236293; COSMIC: COSV52236293;