17-44170809-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_080863.5(ASB16):​c.20C>T​(p.Pro7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Consequence

ASB16
NM_080863.5 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.89
Variant links:
Genes affected
ASB16 (HGNC:19768): (ankyrin repeat and SOCS box containing 16) 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. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17052111).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ASB16NM_080863.5 linkc.20C>T p.Pro7Leu missense_variant Exon 1 of 5 ENST00000293414.6 NP_543139.4 Q96NS5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ASB16ENST00000293414.6 linkc.20C>T p.Pro7Leu missense_variant Exon 1 of 5 1 NM_080863.5 ENSP00000293414.1 Q96NS5
ASB16ENST00000589618.1 linkn.20C>T non_coding_transcript_exon_variant Exon 1 of 5 1 ENSP00000466033.1 K7ELE0
ASB16ENST00000591700.1 linkc.-195-38C>T intron_variant Intron 1 of 2 4 ENSP00000466349.1 K7EM41

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
29
GnomAD4 genome
Cov.:
31

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 26, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.20C>T (p.P7L) alteration is located in exon 1 (coding exon 1) of the ASB16 gene. This alteration results from a C to T substitution at nucleotide position 20, causing the proline (P) at amino acid position 7 to be replaced by a leucine (L). 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
Benign
0.13
BayesDel_addAF
Benign
-0.033
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
20
DANN
Uncertain
1.0
DEOGEN2
Benign
0.083
T
Eigen
Benign
-0.42
Eigen_PC
Benign
-0.27
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Benign
0.71
T
M_CAP
Benign
0.034
D
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Uncertain
0.52
T
PROVEAN
Uncertain
-4.0
D
REVEL
Benign
0.13
Sift
Benign
0.17
T
Sift4G
Uncertain
0.011
D
Polyphen
0.049
B
Vest4
0.40
MutPred
0.33
Gain of MoRF binding (P = 0.0619);
MVP
0.62
MPC
0.33
ClinPred
0.91
D
GERP RS
3.3
Varity_R
0.25
gMVP
0.51

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: rs2054235880; hg19: chr17-42248177; API