dbSNP rs11200251: ATE1:c.337+99G>A (chr10-121913691-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001001976.3(ATE1):c.337+99G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 753,452 control chromosomes in the GnomAD database, including 42,405 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 0.30 ( 7119 hom., cov: 32)

Exomes 𝑓: 0.34 ( 35286 hom. )

Consequence

ATE1
NM_001001976.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0980

Publications

10 publications found

Variant links:

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

ATE1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 = 0.415 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATE1	NM_001001976.3	MANE Select	c.337+99G>A	intron	N/A	NP_001001976.1	O95260-1
ATE1	NM_001439361.1		c.388+99G>A	intron	N/A	NP_001426290.1
ATE1	NM_001437419.1		c.337+99G>A	intron	N/A	NP_001424348.1	A0A8I5KZ24

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ATE1	ENST00000224652.12	TSL:1 MANE Select	c.337+99G>A	intron	N/A	ENSP00000224652.6	O95260-1
ATE1	ENST00000369043.8	TSL:1	c.337+99G>A	intron	N/A	ENSP00000358039.3	O95260-2
ATE1	ENST00000423243.7	TSL:1	n.*54+99G>A	intron	N/A	ENSP00000397787.2	H0Y5C2

Frequencies

GnomAD3 genomes

AF:

0.296

AC:

44882

AN:

151880

Hom.:

7105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.426

Gnomad AMR

AF:

0.351

Gnomad ASJ

AF:

0.298

Gnomad EAS

AF:

0.293

Gnomad SAS

AF:

0.430

Gnomad FIN

AF:

0.306

Gnomad MID

AF:

0.321

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.303

GnomAD4 exome

AF:

0.339

AC:

203880

AN:

601454

Hom.:

35286

AF XY:

0.343

AC XY:

107670

AN XY:

313688

show subpopulations

African (AFR)

AF:

0.164

AC:

2510

AN:

15274

American (AMR)

AF:

0.362

AC:

9320

AN:

25742

Ashkenazi Jewish (ASJ)

AF:

0.284

AC:

4365

AN:

15346

East Asian (EAS)

AF:

0.314

AC:

10273

AN:

32766

South Asian (SAS)

AF:

0.418

AC:

21318

AN:

50974

European-Finnish (FIN)

AF:

0.300

AC:

14141

AN:

47120

Middle Eastern (MID)

AF:

0.327

AC:

1265

AN:

3870

European-Non Finnish (NFE)

AF:

0.345

AC:

130831

AN:

379338

Other (OTH)

AF:

0.318

AC:

9857

AN:

31024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

6308

12617

18925

25234

31542

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2064

4128

6192

8256

10320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.296

AC:

44923

AN:

151998

Hom.:

7119

Cov.:

AF XY:

0.298

AC XY:

22157

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.169

AC:

7028

AN:

41492

American (AMR)

AF:

0.352

AC:

5367

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.298

AC:

1035

AN:

3472

East Asian (EAS)

AF:

0.292

AC:

1504

AN:

5148

South Asian (SAS)

AF:

0.431

AC:

2076

AN:

4818

European-Finnish (FIN)

AF:

0.306

AC:

3231

AN:

10544

Middle Eastern (MID)

AF:

0.328

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.347

AC:

23565

AN:

67950

Other (OTH)

AF:

0.301

AC:

635

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1585

3169

4754

6338

7923

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

464

928

1392

1856

2320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.322

Hom.:

3238

Bravo

AF:

0.288

Asia WGS

AF:

0.327

AC:

1138

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.5

(source)

DANN

Benign

0.80

PhyloP100

0.098

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over