NM_080873.3:c.529G>C

Variant names:

• chrX-15289630-C-G
• rs140433192
• NM_080873.3:c.529G>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_080873.3(ASB11):​c.529G>C​(p.Glu177Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000348 in 1,206,072 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign 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. E177K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000037 (0 hom. 12 hem.)
• Consequence: ASB11 NM_080873.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.81
• Publications: 1 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3249696).
• BS2: High Hemizygotes in GnomAdExome4 at 12 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.529G>C	p.Glu177Gln	missense	Exon 5 of 7	NP_543149.1	Q8WXH4-1
	ASB11	NM_001201583.2		c.478G>C	p.Glu160Gln	missense	Exon 5 of 7	NP_001188512.1	Q8WXH4-2
	ASB11	NM_001012428.2		c.466G>C	p.Glu156Gln	missense	Exon 5 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.529G>C	p.Glu177Gln	missense	Exon 5 of 7	ENSP00000417914.1	Q8WXH4-1
	ASB11	ENST00000380470.7	TSL:1	c.478G>C	p.Glu160Gln	missense	Exon 5 of 7	ENSP00000369837.3	Q8WXH4-2
	ASB11	ENST00000485437.2	TSL:1	n.647G>C		non_coding_transcript_exon	Exon 6 of 8	ENSP00000419385.2	F8WF31

Frequencies

GnomAD3 genomes AF: 0.00000895 AC: 1 AN: 111674 Hom.: 0 Cov.: 23

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000389 AC: 7 AN: 180140 AF XY: 0.0000618

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000865

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000375 AC: 41 AN: 1094398 Hom.: 0 Cov.: 29 AF XY: 0.0000333 AC XY: 12 AN XY: 359942

African (AFR) AF: 0.00 AC: 0 AN: 26279

American (AMR) AF: 0.00 AC: 0 AN: 34745

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19261

East Asian (EAS) AF: 0.00 AC: 0 AN: 30153

South Asian (SAS) AF: 0.00 AC: 0 AN: 53313

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4121

European-Non Finnish (NFE) AF: 0.0000488 AC: 41 AN: 840081

Other (OTH) AF: 0.00 AC: 0 AN: 45969

GnomAD4 genome AF: 0.00000895 AC: 1 AN: 111674 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33860

African (AFR) AF: 0.00 AC: 0 AN: 30686

American (AMR) AF: 0.00 AC: 0 AN: 10467

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2643

East Asian (EAS) AF: 0.00 AC: 0 AN: 3570

South Asian (SAS) AF: 0.00 AC: 0 AN: 2687

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6019

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53175

Other (OTH) AF: 0.00 AC: 0 AN: 1500

Alfa AF: 0.00000820 Hom.: 1

Bravo AF: 0.0000113

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000346 AC: 1

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.0000548

EpiControl AF: 0.000119

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	Benign	0.12
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	T
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.32	T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.8
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.16
Sift	Benign	0.10	T
Sift4G	Benign	0.14	T
Polyphen		1.0	D
Vest4		0.27
MutPred		0.39		Loss of loop (P = 0.1242)
MVP		0.72
MPC		0.046
ClinPred		0.14	T
GERP RS		4.7
Varity_R		0.40
gMVP		0.39
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs140433192; hg19: chrX-15307752;