10-121812677-G-C

Variant names:

• chr10-121812677-G-C
• rs12718345
• NM_001001976.3:c.1258-22388C>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.1258-22388C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 152,012 control chromosomes in the GnomAD database, including 24,403 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 0.56 (24403 hom., cov: 33)
• Consequence: ATE1 NM_001001976.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 1 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 (AFR) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATE1	NM_001001976.3	c.1258-22388C>G		intron_variant	Intron 10 of 11	ENST00000224652.12	NP_001001976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATE1	ENST00000224652.12	c.1258-22388C>G		intron_variant	Intron 10 of 11	1	NM_001001976.3	ENSP00000224652.6

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85392 AN: 151894 Hom.: 24383 Cov.: 33

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.550

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.562 AC: 85459 AN: 152012 Hom.: 24403 Cov.: 33 AF XY: 0.558 AC XY: 41455 AN XY: 74288

African (AFR) AF: 0.641 AC: 26557 AN: 41462

American (AMR) AF: 0.527 AC: 8047 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1620 AN: 3468

East Asian (EAS) AF: 0.328 AC: 1696 AN: 5164

South Asian (SAS) AF: 0.551 AC: 2656 AN: 4816

European-Finnish (FIN) AF: 0.540 AC: 5693 AN: 10540

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.550 AC: 37411 AN: 67968

Other (OTH) AF: 0.540 AC: 1140 AN: 2112

Alfa AF: 0.570 Hom.: 3126

Bravo AF: 0.562

Asia WGS AF: 0.438 AC: 1523 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	0.58
DANN	Benign	0.82
PhyloP100		-1.0
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: rs12718345; hg19: chr10-123572192;