Genetic Variant NM_001001976.3:c.1141G>A (chr10-121841098-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001001976.3(ATE1):c.1141G>A(p.Val381Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000685 in 1,562,440 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000069 ( 1 hom. )

Consequence

ATE1
NM_001001976.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.30

Publications

3 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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.090883136).

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	HGVSp	Effect	Exon Rank	Protein	UniProt
ATE1	NM_001001976.3	MANE Select	c.1141G>A	p.Val381Ile	missense	Exon 9 of 12	NP_001001976.1	O95260-1
ATE1	NM_001439361.1		c.1321G>A	p.Val441Ile	missense	Exon 10 of 13	NP_001426290.1
ATE1	NM_001437419.1		c.1270G>A	p.Val424Ile	missense	Exon 10 of 13	NP_001424348.1	A0A8I5KZ24

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATE1	ENST00000224652.12	TSL:1 MANE Select	c.1141G>A	p.Val381Ile	missense	Exon 9 of 12	ENSP00000224652.6	O95260-1
ATE1	ENST00000369043.8	TSL:1	c.1141G>A	p.Val381Ile	missense	Exon 9 of 12	ENSP00000358039.3	O95260-2
ATE1	ENST00000423243.7	TSL:1	n.*858G>A		non_coding_transcript_exon	Exon 7 of 10	ENSP00000397787.2	H0Y5C2

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

151966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00125

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000156

AC:

AN:

237860

AF XY:

0.000194

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000590

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000555

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000688

AC:

AN:

1410356

Hom.:

Cov.:

AF XY:

0.0000928

AC XY:

AN XY:

700702

show subpopulations

African (AFR)

AF:

0.000124

AC:

AN:

32164

American (AMR)

AF:

0.00

AC:

AN:

42708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24758

East Asian (EAS)

AF:

0.0000261

AC:

AN:

38294

South Asian (SAS)

AF:

0.000910

AC:

AN:

76922

European-Finnish (FIN)

AF:

0.0000196

AC:

AN:

50970

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5568

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

1081234

Other (OTH)

AF:

0.0000866

AC:

AN:

57738

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0000658

AC:

AN:

152084

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41510

American (AMR)

AF:

0.0000655

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00125

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10536

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68004

Other (OTH)

AF:

0.00

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000330

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.0041

MetaRNN

Benign

0.091

MetaSVM

Benign

-0.38

MutationAssessor

Benign

2.0

PhyloP100

3.3

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.90

REVEL

Benign

0.16

Sift

Uncertain

0.013

Sift4G

Uncertain

0.016

Polyphen

0.98

Vest4

0.23

MutPred

0.69

Loss of phosphorylation at Y382 (P = 0.1497)

MVP

0.15

MPC

0.13

ClinPred

0.15

GERP RS

5.6

PromoterAI

0.00040

Neutral

(source)

Varity_R

0.13

gMVP

0.36

Mutation Taster

=93/7

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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