X-15287961-C-A

Variant names:

• chrX-15287961-C-A
• NM_080873.3:c.767G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.560

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]

ACMG classification

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
ASB11	NM_080873.3	c.767G>T	p.Arg256Leu	missense_variant	Exon 6 of 7	ENST00000480796.6	NP_543149.1
ASB11	NM_001201583.2	c.716G>T	p.Arg239Leu	missense_variant	Exon 6 of 7		NP_001188512.1
ASB11	NM_001012428.2	c.704G>T	p.Arg235Leu	missense_variant	Exon 6 of 7		NP_001012428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB11	ENST00000480796.6	c.767G>T	p.Arg256Leu	missense_variant	Exon 6 of 7	1	NM_080873.3	ENSP00000417914.1

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

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;