10-5666541-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024701.4(ASB13):​c.11G>A​(p.Arg4Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000218 in 1,240,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

ASB13
NM_024701.4 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.167
Variant links:
Genes affected
ASB13 (HGNC:19765): (ankyrin repeat and SOCS box containing 13) The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. They contain ankyrin repeat sequence and a SOCS box domain. The SOCS box serves to couple suppressor of cytokine signalling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. Multiple alternatively spliced transcript variants, both protein-coding and not protein-coding, have been described for this gene. [provided by RefSeq, Nov 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14132312).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ASB13NM_024701.4 linkc.11G>A p.Arg4Gln missense_variant Exon 1 of 6 ENST00000357700.11 NP_078977.2 Q8WXK3-1
ASB13NR_024581.2 linkn.55G>A non_coding_transcript_exon_variant Exon 1 of 5
ASB13NR_037164.2 linkn.55G>A non_coding_transcript_exon_variant Exon 1 of 7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ASB13ENST00000357700.11 linkc.11G>A p.Arg4Gln missense_variant Exon 1 of 6 1 NM_024701.4 ENSP00000350331.6 Q8WXK3-1
ASB13ENST00000459912.5 linkn.11G>A non_coding_transcript_exon_variant Exon 1 of 7 1 ENSP00000433358.1 Q8WXK3-2
ASB13ENST00000479033.1 linkn.55G>A non_coding_transcript_exon_variant Exon 1 of 5 2

Frequencies

GnomAD3 genomes
AF:
0.000133
AC:
20
AN:
150704
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000484
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000643
AC:
7
AN:
1089462
Hom.:
0
Cov.:
31
AF XY:
0.0000114
AC XY:
6
AN XY:
524242
show subpopulations
Gnomad4 AFR exome
AF:
0.000272
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000316
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.000133
AC:
20
AN:
150812
Hom.:
0
Cov.:
33
AF XY:
0.0000543
AC XY:
4
AN XY:
73662
show subpopulations
Gnomad4 AFR
AF:
0.000483
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.000132

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 26, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.11G>A (p.R4Q) alteration is located in exon 1 (coding exon 1) of the ASB13 gene. This alteration results from a G to A substitution at nucleotide position 11, causing the arginine (R) at amino acid position 4 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
0.13
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
15
DANN
Uncertain
1.0
DEOGEN2
Benign
0.037
T
Eigen
Benign
-0.83
Eigen_PC
Benign
-0.87
FATHMM_MKL
Benign
0.068
N
LIST_S2
Benign
0.57
T
M_CAP
Uncertain
0.20
D
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.46
N
PrimateAI
Pathogenic
0.79
T
PROVEAN
Benign
-0.62
N
REVEL
Benign
0.036
Sift
Benign
0.15
T
Sift4G
Benign
0.085
T
Polyphen
0.64
P
Vest4
0.22
MutPred
0.42
Loss of helix (P = 0.2022);
MVP
0.46
MPC
0.16
ClinPred
0.11
T
GERP RS
2.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.045
gMVP
0.26

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: rs902756198; hg19: chr10-5708504; API