4-176225269-A-G
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_080874.4(ASB5):āc.269T>Cā(p.Leu90Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,459,418 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 (ā ).
Frequency
Genomes: not found (cov: 33)
Exomes š: 0.000019 ( 0 hom. )
Consequence
ASB5
NM_080874.4 missense
NM_080874.4 missense
Scores
9
8
2
Clinical Significance
Conservation
PhyloP100: 8.37
Genes affected
ASB5 (HGNC:17180): (ankyrin repeat and SOCS box containing 5) 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 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 have been described for this gene but their full length sequences are not known. [provided by RefSeq, Jul 2008]
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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, 0.95
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ASB5 | NM_080874.4 | c.269T>C | p.Leu90Ser | missense_variant | 2/7 | ENST00000296525.7 | |
ASB5 | NM_001410863.1 | c.134T>C | p.Leu45Ser | missense_variant | 2/7 | ||
ASB5 | XM_005262759.2 | c.269T>C | p.Leu90Ser | missense_variant | 4/9 | ||
ASB5 | XM_011531617.4 | c.110T>C | p.Leu37Ser | missense_variant | 2/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ASB5 | ENST00000296525.7 | c.269T>C | p.Leu90Ser | missense_variant | 2/7 | 1 | NM_080874.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
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33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251404Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135876
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GnomAD4 exome AF: 0.0000192 AC: 28AN: 1459418Hom.: 0 Cov.: 30 AF XY: 0.0000207 AC XY: 15AN XY: 726258
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GnomAD4 genome Cov.: 33
GnomAD4 genome
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33
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 submitter | clinical testing | Ambry Genetics | Aug 30, 2022 | The c.269T>C (p.L90S) alteration is located in exon 2 (coding exon 2) of the ASB5 gene. This alteration results from a T to C substitution at nucleotide position 269, causing the leucine (L) at amino acid position 90 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MutPred
Loss of stability (P = 0.0961);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at