10-121871925-G-C

Variant names:

• chr10-121871925-G-C
• rs10887005
• NM_001001976.3:c.943-1887C>G

Variant summary

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

The NM_001001976.3(ATE1):​c.943-1887C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,070 control chromosomes in the GnomAD database, including 6,605 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 0.27 (6605 hom., cov: 32)
• Consequence: ATE1 NM_001001976.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230
• Publications: 8 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATE1	NM_001001976.3	c.943-1887C>G		intron_variant	Intron 7 of 11	ENST00000224652.12	NP_001001976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATE1	ENST00000224652.12	c.943-1887C>G		intron_variant	Intron 7 of 11	1	NM_001001976.3	ENSP00000224652.6

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41165 AN: 151950 Hom.: 6601 Cov.: 32

Gnomad AFR AF: 0.0844

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.271 AC: 41172 AN: 152070 Hom.: 6605 Cov.: 32 AF XY: 0.274 AC XY: 20386 AN XY: 74328

African (AFR) AF: 0.0842 AC: 3494 AN: 41512

American (AMR) AF: 0.343 AC: 5238 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1031 AN: 3470

East Asian (EAS) AF: 0.291 AC: 1505 AN: 5170

South Asian (SAS) AF: 0.430 AC: 2072 AN: 4820

European-Finnish (FIN) AF: 0.308 AC: 3242 AN: 10538

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23522 AN: 67956

Other (OTH) AF: 0.277 AC: 585 AN: 2110

Alfa AF: 0.299 Hom.: 965

Bravo AF: 0.260

Asia WGS AF: 0.315 AC: 1096 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.72
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10887005; hg19: chr10-123631440; COSMIC: COSV56443880;