7-151176164-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong
The NM_001142459.2(ASB10):c.1352C>T(p.Pro451Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,611,688 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000012 ( 1 hom. )
Consequence
ASB10
NM_001142459.2 missense
NM_001142459.2 missense
Scores
13
2
2
Clinical Significance
Conservation
PhyloP100: 9.79
Genes affected
ASB10 (HGNC:17185): (ankyrin repeat and SOCS box containing 10) The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. The SOCS box serves to couple suppressor of cytokine signaling (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. [provided by RefSeq, Dec 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.95
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ASB10 | NM_001142459.2 | c.1352C>T | p.Pro451Leu | missense_variant | 5/6 | ENST00000420175.3 | |
ASB10 | NM_080871.4 | c.1307C>T | p.Pro436Leu | missense_variant | 5/6 | ||
ASB10 | NM_001142460.1 | c.1238C>T | p.Pro413Leu | missense_variant | 4/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ASB10 | ENST00000420175.3 | c.1352C>T | p.Pro451Leu | missense_variant | 5/6 | 1 | NM_001142459.2 | P4 | |
ASB10 | ENST00000275838.5 | c.1238C>T | p.Pro413Leu | missense_variant | 4/5 | 1 | |||
ASB10 | ENST00000377867.7 | c.1307C>T | p.Pro436Leu | missense_variant | 5/6 | 2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152192Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000122 AC: 3AN: 245076Hom.: 0 AF XY: 0.00000748 AC XY: 1AN XY: 133746
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GnomAD4 exome AF: 0.0000123 AC: 18AN: 1459496Hom.: 1 Cov.: 31 AF XY: 0.00000826 AC XY: 6AN XY: 726066
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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 | Oct 20, 2023 | The c.1352C>T (p.P451L) alteration is located in exon 5 (coding exon 5) of the ASB10 gene. This alteration results from a C to T substitution at nucleotide position 1352, causing the proline (P) at amino acid position 451 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
1.0
.;D;D
Vest4
MVP
MPC
0.34
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