10-121865675-T-C

Variant names:

• chr10-121865675-T-C
• rs10510102
• NM_001001976.3:c.975+4331A>G

Variant summary

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

The NM_001439361.1(ATE1):​c.1155+4331A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,084 control chromosomes in the GnomAD database, including 2,264 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 0.17 (2264 hom., cov: 32)
• Consequence: ATE1 NM_001439361.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0230
• Publications: 37 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=-0.64).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001439361.1. 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
	ATE1	NM_001001976.3	MANE Select	c.975+4331A>G		intron	N/A	NP_001001976.1
	ATE1	NM_001439361.1		c.1155+4331A>G		intron	N/A	NP_001426290.1
	ATE1	NM_001437419.1		c.1104+4331A>G		intron	N/A	NP_001424348.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATE1	ENST00000224652.12	TSL:1 MANE Select	c.975+4331A>G		intron	N/A	ENSP00000224652.6
	ATE1	ENST00000369043.8	TSL:1	c.975+4331A>G		intron	N/A	ENSP00000358039.3
	ATE1	ENST00000423243.7	TSL:1	n.*692+4331A>G		intron	N/A	ENSP00000397787.2

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26194 AN: 151966 Hom.: 2262 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.172 AC: 26204 AN: 152084 Hom.: 2264 Cov.: 32 AF XY: 0.171 AC XY: 12678 AN XY: 74336

African (AFR) AF: 0.160 AC: 6647 AN: 41488

American (AMR) AF: 0.153 AC: 2342 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 964 AN: 3472

East Asian (EAS) AF: 0.185 AC: 955 AN: 5154

South Asian (SAS) AF: 0.101 AC: 488 AN: 4830

European-Finnish (FIN) AF: 0.161 AC: 1700 AN: 10568

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12486 AN: 67992

Other (OTH) AF: 0.198 AC: 417 AN: 2104

Alfa AF: 0.183 Hom.: 12205

Bravo AF: 0.173

Asia WGS AF: 0.139 AC: 482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.9
DANN	Benign	0.70
PhyloP100		-0.023
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: rs10510102; hg19: chr10-123625190;