rs376093669

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_024701.4(ASB13):​c.418G>T​(p.Gly140Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G140R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

ASB13
NM_024701.4 missense

Scores

11
5
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.52
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.919

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ASB13NM_024701.4 linkc.418G>T p.Gly140Trp missense_variant Exon 4 of 6 ENST00000357700.11 NP_078977.2 Q8WXK3-1
ASB13NR_024581.2 linkn.311G>T non_coding_transcript_exon_variant Exon 3 of 5
ASB13NR_037164.2 linkn.462G>T non_coding_transcript_exon_variant Exon 4 of 7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ASB13ENST00000357700.11 linkc.418G>T p.Gly140Trp missense_variant Exon 4 of 6 1 NM_024701.4 ENSP00000350331.6 Q8WXK3-1
ASB13ENST00000459912.5 linkn.418G>T non_coding_transcript_exon_variant Exon 4 of 7 1 ENSP00000433358.1 Q8WXK3-2
ASB13ENST00000479033.1 linkn.311G>T non_coding_transcript_exon_variant Exon 3 of 5 2
ASB13ENST00000482921.1 linkn.392G>T non_coding_transcript_exon_variant Exon 2 of 2 3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.97
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.10
CADD
Pathogenic
29
DANN
Uncertain
0.99
DEOGEN2
Benign
0.38
T
Eigen
Pathogenic
0.70
Eigen_PC
Uncertain
0.56
FATHMM_MKL
Benign
0.67
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Pathogenic
0.57
D
MetaRNN
Pathogenic
0.92
D
MetaSVM
Uncertain
0.61
D
MutationAssessor
Pathogenic
4.0
H
PrimateAI
Uncertain
0.78
T
PROVEAN
Pathogenic
-6.9
D
REVEL
Pathogenic
0.78
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.75
MutPred
0.71
Loss of catalytic residue at G140 (P = 0.1072);
MVP
0.81
MPC
0.65
ClinPred
1.0
D
GERP RS
4.7
Varity_R
0.85
gMVP
0.69

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-5691032; API