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. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate 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
• Publications: 20 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 (REVEL=0.043).
• BP6: Variant 10-121836739-T-C is Benign according to our data. Variant chr10-121836739-T-C is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001001976.3. 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.1236A>G	p.Ser412Ser	synonymous	Exon 10 of 12	NP_001001976.1	O95260-1
	ATE1	NM_001439361.1		c.1416A>G	p.Ser472Ser	synonymous	Exon 11 of 13	NP_001426290.1
	ATE1	NM_001437419.1		c.1365A>G	p.Ser455Ser	synonymous	Exon 11 of 13	NP_001424348.1	A0A8I5KZ24

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATE1	ENST00000224652.12	TSL:1 MANE Select	c.1236A>G	p.Ser412Ser	synonymous	Exon 10 of 12	ENSP00000224652.6	O95260-1
	ATE1	ENST00000369043.8	TSL:1	c.1236A>G	p.Ser412Ser	synonymous	Exon 10 of 12	ENSP00000358039.3	O95260-2
	ATE1	ENST00000423243.7	TSL:1	n.*953A>G		non_coding_transcript_exon	Exon 8 of 10	ENSP00000397787.2	H0Y5C2

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

GnomAD2 exomes AF: 0.896 AC: 209383 AN: 233738 AF XY: 0.901

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 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

African (AFR) AF: 0.871 AC: 27600 AN: 31692

American (AMR) AF: 0.767 AC: 30660 AN: 39954

Ashkenazi Jewish (ASJ) AF: 0.952 AC: 24296 AN: 25530

East Asian (EAS) AF: 0.923 AC: 35932 AN: 38938

South Asian (SAS) AF: 0.890 AC: 71556 AN: 80402

European-Finnish (FIN) AF: 0.931 AC: 49568 AN: 53248

Middle Eastern (MID) AF: 0.940 AC: 5059 AN: 5382

European-Non Finnish (NFE) AF: 0.921 AC: 1002537 AN: 1089028

Other (OTH) AF: 0.914 AC: 53842 AN: 58900

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

African (AFR) AF: 0.872 AC: 36191 AN: 41526

American (AMR) AF: 0.822 AC: 12558 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.953 AC: 3310 AN: 3472

East Asian (EAS) AF: 0.931 AC: 4819 AN: 5176

South Asian (SAS) AF: 0.891 AC: 4296 AN: 4820

European-Finnish (FIN) AF: 0.931 AC: 9856 AN: 10588

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.924 AC: 62884 AN: 68022

Other (OTH) AF: 0.903 AC: 1909 AN: 2114

Alfa AF: 0.913 Hom.: 98008

Bravo AF: 0.889

Asia WGS AF: 0.881 AC: 3060 AN: 3470

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ATE1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.2
DANN	Benign	0.60
PhyloP100		-1.6
Mutation Taster		=98/2	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: rs4237536; hg19: chr10-123596254; COSMIC: COSV108079934; COSMIC: COSV108079934;