10-5652906-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_024701.4(ASB13):​c.188G>A​(p.Gly63Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000021 in 1,431,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ASB13
NM_024701.4 missense

Scores

7
7
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.82
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 Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.959

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ASB13NM_024701.4 linkc.188G>A p.Gly63Asp missense_variant Exon 2 of 6 ENST00000357700.11 NP_078977.2 Q8WXK3-1
ASB13NR_024581.2 linkn.232G>A non_coding_transcript_exon_variant Exon 2 of 5
ASB13NR_037164.2 linkn.232G>A non_coding_transcript_exon_variant Exon 2 of 7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ASB13ENST00000357700.11 linkc.188G>A p.Gly63Asp missense_variant Exon 2 of 6 1 NM_024701.4 ENSP00000350331.6 Q8WXK3-1
ASB13ENST00000459912.5 linkn.188G>A non_coding_transcript_exon_variant Exon 2 of 7 1 ENSP00000433358.1 Q8WXK3-2
ASB13ENST00000479033.1 linkn.232G>A non_coding_transcript_exon_variant Exon 2 of 5 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000210
AC:
3
AN:
1431904
Hom.:
0
Cov.:
30
AF XY:
0.00000282
AC XY:
2
AN XY:
709094
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000247
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000245
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 27, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.188G>A (p.G63D) alteration is located in exon 2 (coding exon 2) of the ASB13 gene. This alteration results from a G to A substitution at nucleotide position 188, causing the glycine (G) at amino acid position 63 to be replaced by an aspartic acid (D). 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
Pathogenic
0.92
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Pathogenic
0.14
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
T
Eigen
Pathogenic
0.69
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.83
T
M_CAP
Uncertain
0.11
D
MetaRNN
Pathogenic
0.96
D
MetaSVM
Uncertain
-0.16
T
MutationAssessor
Uncertain
2.3
M
PrimateAI
Uncertain
0.70
T
PROVEAN
Pathogenic
-5.3
D
REVEL
Uncertain
0.52
Sift
Benign
0.32
T
Sift4G
Benign
0.44
T
Polyphen
0.95
P
Vest4
0.77
MutPred
0.87
Gain of solvent accessibility (P = 0.1583);
MVP
0.75
MPC
0.68
ClinPred
1.0
D
GERP RS
5.0
Varity_R
0.62
gMVP
0.67

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: rs1313243479; hg19: chr10-5694869; COSMIC: COSV63091017; COSMIC: COSV63091017; API