3-131024880-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000264992.8(ASTE1):​c.427C>T​(p.Arg143Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ASTE1
ENST00000264992.8 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.36
Variant links:
Genes affected
ASTE1 (HGNC:25021): (asteroid homolog 1) Predicted to enable nuclease activity. Predicted to be involved in nucleic acid phosphodiester bond hydrolysis. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.28217828).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ASTE1NM_014065.4 linkuse as main transcriptc.427C>T p.Arg143Trp missense_variant 3/6 ENST00000264992.8 NP_054784.2 Q2TB18-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ASTE1ENST00000264992.8 linkuse as main transcriptc.427C>T p.Arg143Trp missense_variant 3/61 NM_014065.4 ENSP00000264992.3 Q2TB18-1
ASTE1ENST00000514044.5 linkuse as main transcriptc.427C>T p.Arg143Trp missense_variant 3/71 ENSP00000426421.1 D6RG30
ASTE1ENST00000507978.5 linkuse as main transcriptn.427C>T non_coding_transcript_exon_variant 3/72 ENSP00000421019.1 Q2TB18-2
ASTE1ENST00000504964.1 linkuse as main transcriptn.143+284C>T intron_variant 3 ENSP00000426363.1 D6RGH3

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152056
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251352
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135860
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461864
Hom.:
0
Cov.:
31
AF XY:
0.00000550
AC XY:
4
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152056
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74274
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 12, 2021The c.427C>T (p.R143W) alteration is located in exon 3 (coding exon 1) of the ASTE1 gene. This alteration results from a C to T substitution at nucleotide position 427, causing the arginine (R) at amino acid position 143 to be replaced by a tryptophan (W). 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
0.15
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.030
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.081
T;T
Eigen
Benign
0.11
Eigen_PC
Benign
0.22
FATHMM_MKL
Uncertain
0.76
D
LIST_S2
Uncertain
0.87
D;D
M_CAP
Benign
0.0055
T
MetaRNN
Benign
0.28
T;T
MetaSVM
Benign
-0.81
T
MutationAssessor
Benign
1.9
.;L
MutationTaster
Benign
0.95
D;D
PrimateAI
Benign
0.33
T
PROVEAN
Uncertain
-2.7
D;D
REVEL
Benign
0.12
Sift
Benign
0.15
T;T
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.45
B;B
Vest4
0.39
MutPred
0.51
Gain of catalytic residue at M146 (P = 0.0054);Gain of catalytic residue at M146 (P = 0.0054);
MVP
0.65
MPC
0.65
ClinPred
0.92
D
GERP RS
4.6
Varity_R
0.16
gMVP
0.68

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs766215426; hg19: chr3-130743724; API