10-121902393-C-G

Position:

• chr10-121902393-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001001976.3(ATE1):​c.811G>C​(p.Glu271Gln) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATE1 NM_001001976.3 missense, splice_region
• Scores: Splicing: ADA: 0.9498
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.58

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATE1	NM_001001976.3	c.811G>C	p.Glu271Gln	missense_variant, splice_region_variant	6/12	ENST00000224652.12	NP_001001976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATE1	ENST00000224652.12	c.811G>C	p.Glu271Gln	missense_variant, splice_region_variant	6/12	1	NM_001001976.3	ENSP00000224652	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 20, 2024

The c.811G>C (p.E271Q) alteration is located in exon 6 (coding exon 6) of the ATE1 gene. This alteration results from a G to C substitution at nucleotide position 811, causing the glutamic acid (E) at amino acid position 271 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T;T;T;T;.
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.55	D;D;D;D;D
MetaSVM	Benign	-0.32	T
MutationAssessor	Uncertain	2.8	M;.;.;.;M
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.9	N;N;N;N;N
REVEL	Benign	0.18
Sift	Benign	0.043	D;T;D;D;D
Sift4G	Uncertain	0.054	T;T;T;T;T
Polyphen		0.77	P;B;.;P;D
Vest4		0.59
MutPred		0.63		Gain of MoRF binding (P = 0.0273);.;.;.;Gain of MoRF binding (P = 0.0273);
MVP		0.27
MPC		0.56
ClinPred		0.97	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.31
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.95
dbscSNV1_RF	Pathogenic	0.79
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: rs1951016259; hg19: chr10-123661908;