NM_001001976.3:c.1236A>G

Variant names:

• chr10-121836739-T-C
• rs4237536
• NM_001001976.3:c.1236A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001001976.3(ATE1):​c.1236A>G​(p.Ser412Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.913 in 1,575,284 control chromosomes in the GnomAD database, including 657,356 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.90 (61808 hom., cov: 32)
  • Exomes 𝑓: 0.91 (595548 hom.)
• Consequence: ATE1 NM_001001976.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.59

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 10-121836739-T-C is Benign according to our data. Variant chr10-121836739-T-C is described in ClinVar as [Benign]. Clinvar id is 3060294.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.59 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATE1	NM_001001976.3	c.1236A>G	p.Ser412Ser	synonymous_variant	Exon 10 of 12	ENST00000224652.12	NP_001001976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATE1	ENST00000224652.12	c.1236A>G	p.Ser412Ser	synonymous_variant	Exon 10 of 12	1	NM_001001976.3	ENSP00000224652.6

Frequencies

GnomAD3 genomes AF: 0.900 AC: 136883 AN: 152092 Hom.: 61770 Cov.: 32

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.954

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.953

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.891

Gnomad FIN AF: 0.931

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.924

Gnomad OTH AF: 0.905

GnomAD3 exomes AF: 0.896 AC: 209383 AN: 233738 Hom.: 94265 AF XY: 0.901 AC XY: 114024 AN XY: 126538

Gnomad AFR exome AF: 0.862

Gnomad AMR exome AF: 0.759

Gnomad ASJ exome AF: 0.950

Gnomad EAS exome AF: 0.934

Gnomad SAS exome AF: 0.887

Gnomad FIN exome AF: 0.928

Gnomad NFE exome AF: 0.922

Gnomad OTH exome AF: 0.915

GnomAD4 exome AF: 0.914 AC: 1301050 AN: 1423074 Hom.: 595548 Cov.: 28 AF XY: 0.914 AC XY: 647858 AN XY: 708492

Gnomad4 AFR exome AF: 0.871

Gnomad4 AMR exome AF: 0.767

Gnomad4 ASJ exome AF: 0.952

Gnomad4 EAS exome AF: 0.923

Gnomad4 SAS exome AF: 0.890

Gnomad4 FIN exome AF: 0.931

Gnomad4 NFE exome AF: 0.921

Gnomad4 OTH exome AF: 0.914

GnomAD4 genome AF: 0.900 AC: 136976 AN: 152210 Hom.: 61808 Cov.: 32 AF XY: 0.899 AC XY: 66901 AN XY: 74418

Gnomad4 AFR AF: 0.872

Gnomad4 AMR AF: 0.822

Gnomad4 ASJ AF: 0.953

Gnomad4 EAS AF: 0.931

Gnomad4 SAS AF: 0.891

Gnomad4 FIN AF: 0.931

Gnomad4 NFE AF: 0.924

Gnomad4 OTH AF: 0.903

Alfa AF: 0.916 Hom.: 80944

Bravo AF: 0.889

Asia WGS AF: 0.881 AC: 3060 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ATE1-related disorder Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.2
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs4237536; hg19: chr10-123596254;