Genetic Variant NM_001001976.3:c.1001A>G (chr10-121841238-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001001976.3(ATE1):c.1001A>G(p.Asp334Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ATE1
NM_001001976.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.40

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17543).

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.1001A>G	p.Asp334Gly	missense	Exon 9 of 12	NP_001001976.1	O95260-1
ATE1	NM_001439361.1		c.1181A>G	p.Asp394Gly	missense	Exon 10 of 13	NP_001426290.1
ATE1	NM_001437419.1		c.1130A>G	p.Asp377Gly	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.1001A>G	p.Asp334Gly	missense	Exon 9 of 12	ENSP00000224652.6	O95260-1
ATE1	ENST00000369043.8	TSL:1	c.1001A>G	p.Asp334Gly	missense	Exon 9 of 12	ENSP00000358039.3	O95260-2
ATE1	ENST00000423243.7	TSL:1	n.*718A>G		non_coding_transcript_exon	Exon 7 of 10	ENSP00000397787.2	H0Y5C2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1383714

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

686350

African (AFR)

AF:

0.00

AC:

AN:

31924

American (AMR)

AF:

0.00

AC:

AN:

41340

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24232

East Asian (EAS)

AF:

0.00

AC:

AN:

37660

South Asian (SAS)

AF:

0.00

AC:

AN:

70414

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5454

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1066836

Other (OTH)

AF:

0.00

AC:

AN:

56438

GnomAD4 genome

Cov.:

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

0.12

BayesDel_addAF

Benign

-0.083

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.52

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.038

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.0031

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

3.4

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.045

Sift

Benign

0.14

Sift4G

Benign

0.29

Polyphen

0.51

Vest4

0.20

MutPred

0.46

Gain of glycosylation at P333 (P = 0.0587)

MVP

0.14

MPC

0.20

ClinPred

0.68

GERP RS

4.5

PromoterAI

-0.033

Neutral

(source)

Varity_R

0.19

gMVP

0.53

Mutation Taster

=72/28

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over