chrX-15283602-C-A

Variant names:

• chrX-15283602-C-A
• rs758714896
• NM_080873.3:c.875G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3 BS2

The NM_080873.3(ASB11):​c.875G>T​(p.Arg292Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000415 in 1,205,241 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R292C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000091 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.0000037 (0 hom. 2 hem.)
• Consequence: ASB11 NM_080873.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.53
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.822
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080873.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB11	NM_080873.3	MANE Select	c.875G>T	p.Arg292Leu	missense	Exon 7 of 7	NP_543149.1	Q8WXH4-1
	ASB11	NM_001201583.2		c.824G>T	p.Arg275Leu	missense	Exon 7 of 7	NP_001188512.1	Q8WXH4-2
	ASB11	NM_001012428.2		c.812G>T	p.Arg271Leu	missense	Exon 7 of 7	NP_001012428.1	Q8WXH4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB11	ENST00000480796.6	TSL:1 MANE Select	c.875G>T	p.Arg292Leu	missense	Exon 7 of 7	ENSP00000417914.1	Q8WXH4-1
	ASB11	ENST00000380470.7	TSL:1	c.824G>T	p.Arg275Leu	missense	Exon 7 of 7	ENSP00000369837.3	Q8WXH4-2
	ASB11	ENST00000485437.2	TSL:1	n.*318G>T		non_coding_transcript_exon	Exon 8 of 8	ENSP00000419385.2	F8WF31

Frequencies

GnomAD3 genomes AF: 0.00000913 AC: 1 AN: 109523 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000190

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000109 AC: 2 AN: 183268 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000365 AC: 4 AN: 1095718 Hom.: 0 Cov.: 31 AF XY: 0.00000554 AC XY: 2 AN XY: 361218

African (AFR) AF: 0.00 AC: 0 AN: 26357

American (AMR) AF: 0.0000284 AC: 1 AN: 35162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19306

East Asian (EAS) AF: 0.00 AC: 0 AN: 30101

South Asian (SAS) AF: 0.00 AC: 0 AN: 54047

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40331

Middle Eastern (MID) AF: 0.000243 AC: 1 AN: 4121

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 840322

Other (OTH) AF: 0.00 AC: 0 AN: 45971

GnomAD4 genome AF: 0.00000913 AC: 1 AN: 109523 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 31953

African (AFR) AF: 0.00 AC: 0 AN: 30068

American (AMR) AF: 0.00 AC: 0 AN: 10203

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2628

East Asian (EAS) AF: 0.00 AC: 0 AN: 3510

South Asian (SAS) AF: 0.00 AC: 0 AN: 2378

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5767

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 234

European-Non Finnish (NFE) AF: 0.0000190 AC: 1 AN: 52583

Other (OTH) AF: 0.00 AC: 0 AN: 1478

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.28
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Pathogenic	0.43	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Pathogenic	0.88	D
MutationAssessor	Pathogenic	3.9	H
PhyloP100		6.5
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Pathogenic	0.83
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.58
MutPred		0.77		Loss of MoRF binding (P = 0.0052)
MVP		0.92
MPC		0.30
ClinPred		1.0	D
GERP RS		5.7
Varity_R		0.81
gMVP		0.66
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs758714896; hg19: chrX-15301724;