X-15287961-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_080873.3(ASB11):​c.767G>T​(p.Arg256Leu) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R256H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 24)

Consequence

ASB11
NM_080873.3 missense

Scores

1
16

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.560
Variant links:
Genes affected
ASB11 (HGNC:17186): (ankyrin repeat and SOCS box containing 11) 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. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15455505).
BP6
Variant X-15287961-C-A is Benign according to our data. Variant chrX-15287961-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3130092.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ASB11NM_080873.3 linkc.767G>T p.Arg256Leu missense_variant Exon 6 of 7 ENST00000480796.6 NP_543149.1 Q8WXH4-1
ASB11NM_001201583.2 linkc.716G>T p.Arg239Leu missense_variant Exon 6 of 7 NP_001188512.1 Q8WXH4-2
ASB11NM_001012428.2 linkc.704G>T p.Arg235Leu missense_variant Exon 6 of 7 NP_001012428.1 Q8WXH4-3Q7Z670

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ASB11ENST00000480796.6 linkc.767G>T p.Arg256Leu missense_variant Exon 6 of 7 1 NM_080873.3 ENSP00000417914.1 Q8WXH4-1

Frequencies

GnomAD3 genomes
Cov.:
24
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
24

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Dec 28, 2023
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.079
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.77
CADD
Benign
16
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0093
.;.;T
FATHMM_MKL
Benign
0.093
N
LIST_S2
Benign
0.31
T;T;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.15
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.13
.;.;N
PrimateAI
Benign
0.19
T
PROVEAN
Benign
-0.27
N;N;N
REVEL
Benign
0.033
Sift
Benign
0.24
T;T;T
Sift4G
Benign
0.44
T;T;T
Polyphen
0.0
.;.;B
Vest4
0.19
MutPred
0.39
.;.;Loss of MoRF binding (P = 0.0139);
MVP
0.93
MPC
0.044
ClinPred
0.27
T
GERP RS
1.2
Varity_R
0.28
gMVP
0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-15306083; API