NM_001040445.3:c.50G>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001040445.3(ASB1):​c.50G>A​(p.Gly17Asp) variant causes a missense, splice region 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

ASB1
NM_001040445.3 missense, splice_region

Scores

4
8
7
Splicing: ADA: 0.9988
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.64
Variant links:
Genes affected
ASB1 (HGNC:16011): (ankyrin repeat and SOCS box containing 1) The protein encoded by this gene contains an 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, targeting them for ubiquitination and degradation. [provided by RefSeq, Aug 2016]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.77

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ASB1NM_001040445.3 linkc.50G>A p.Gly17Asp missense_variant, splice_region_variant Exon 2 of 5 ENST00000264607.9 NP_001035535.1 Q9Y576
ASB1NM_001330196.2 linkc.50G>A p.Gly17Asp missense_variant, splice_region_variant Exon 2 of 4 NP_001317125.1 B9A047

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ASB1ENST00000264607.9 linkc.50G>A p.Gly17Asp missense_variant, splice_region_variant Exon 2 of 5 1 NM_001040445.3 ENSP00000264607.4 Q9Y576

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 05, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.50G>A (p.G17D) alteration is located in exon 2 (coding exon 2) of the ASB1 gene. This alteration results from a G to A substitution at nucleotide position 50, causing the glycine (G) at amino acid position 17 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
Uncertain
0.50
BayesDel_addAF
Uncertain
0.047
T
BayesDel_noAF
Benign
-0.17
CADD
Pathogenic
29
DANN
Benign
0.97
DEOGEN2
Benign
0.20
T;T
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.64
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.91
D;D
M_CAP
Pathogenic
0.97
D
MetaRNN
Pathogenic
0.77
D;D
MetaSVM
Benign
-0.71
T
MutationAssessor
Benign
0.97
L;.
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
-0.97
N;N
REVEL
Uncertain
0.34
Sift
Uncertain
0.0080
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;.
Vest4
0.56
MutPred
0.43
Gain of relative solvent accessibility (P = 0.0289);Gain of relative solvent accessibility (P = 0.0289);
MVP
0.73
MPC
1.6
ClinPred
0.94
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.50
gMVP
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-239342195; API