ENST00000690984.1:c.437-22670C>G

Variant names:

• chr10-121732153-G-C
• rs2935706
• ENST00000690984.1:c.437-22670C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000690984.1(ATE1):​c.437-22670C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,006 control chromosomes in the GnomAD database, including 6,837 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 0.29 (6837 hom., cov: 32)
• Consequence: ATE1 ENST00000690984.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.472
• Publications: 3 publications found

Genes affected

ATE1 (HGNC:782): (arginyltransferase 1) This gene encodes an arginyltransferase, an enzyme that is involved in posttranslational conjugation of arginine to N-terminal aspartate or glutamate residues. Conjugation of arginine to the N-terminal aspartate or glutamate targets proteins for ubiquitin-dependent degradation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

ATE1 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATE1	ENST00000690984.1	c.437-22670C>G		intron_variant	Intron 4 of 4			ENSP00000510447.1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43603 AN: 151888 Hom.: 6809 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.272

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.287 AC: 43667 AN: 152006 Hom.: 6837 Cov.: 32 AF XY: 0.294 AC XY: 21827 AN XY: 74280

African (AFR) AF: 0.373 AC: 15458 AN: 41474

American (AMR) AF: 0.379 AC: 5786 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 536 AN: 3466

East Asian (EAS) AF: 0.282 AC: 1453 AN: 5150

South Asian (SAS) AF: 0.240 AC: 1152 AN: 4806

European-Finnish (FIN) AF: 0.340 AC: 3586 AN: 10558

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14818 AN: 67966

Other (OTH) AF: 0.280 AC: 588 AN: 2098

Alfa AF: 0.260 Hom.: 715

Bravo AF: 0.293

Asia WGS AF: 0.291 AC: 1008 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.38
DANN	Benign	0.67
PhyloP100		-0.47

Splicing

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

Other links and lift over

dbSNP: rs2935706; hg19: chr10-123491668;