Genetic Variant ASB11:p.Glu177Lys (chrX-15289630-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_080873.3(ASB11):c.529G>A(p.Glu177Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000381 in 1,206,072 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 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. E177Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.000029 ( 0 hom. 10 hem. )

Consequence

ASB11
NM_080873.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.81

Publications

1 publications found

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]

ASB11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.18346974).

BS2

High Hemizygotes in GnomAd4 at 6 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASB11	NM_080873.3	MANE Select	c.529G>A	p.Glu177Lys	missense	Exon 5 of 7	NP_543149.1	Q8WXH4-1
ASB11	NM_001201583.2		c.478G>A	p.Glu160Lys	missense	Exon 5 of 7	NP_001188512.1	Q8WXH4-2
ASB11	NM_001012428.2		c.466G>A	p.Glu156Lys	missense	Exon 5 of 7	NP_001012428.1	Q8WXH4-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASB11	ENST00000480796.6	TSL:1 MANE Select	c.529G>A	p.Glu177Lys	missense	Exon 5 of 7	ENSP00000417914.1	Q8WXH4-1
ASB11	ENST00000380470.7	TSL:1	c.478G>A	p.Glu160Lys	missense	Exon 5 of 7	ENSP00000369837.3	Q8WXH4-2
ASB11	ENST00000485437.2	TSL:1	n.647G>A		non_coding_transcript_exon	Exon 6 of 8	ENSP00000419385.2	F8WF31

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

111674

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000358

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000840

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000999

AC:

AN:

180140

AF XY:

0.0000773

show subpopulations

Gnomad AFR exome

AF:

0.000611

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000660

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000224

GnomAD4 exome

AF:

0.0000292

AC:

AN:

1094398

Hom.:

Cov.:

AF XY:

0.0000278

AC XY:

AN XY:

359942

show subpopulations

African (AFR)

AF:

0.000152

AC:

AN:

26279

American (AMR)

AF:

0.00

AC:

AN:

34745

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19261

East Asian (EAS)

AF:

0.000464

AC:

AN:

30153

South Asian (SAS)

AF:

0.00

AC:

AN:

53313

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40476

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4121

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

840081

Other (OTH)

AF:

0.000305

AC:

AN:

45969

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000125

AC:

AN:

111674

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

AN XY:

33860

show subpopulations

African (AFR)

AF:

0.000358

AC:

AN:

30686

American (AMR)

AF:

0.00

AC:

AN:

10467

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2643

East Asian (EAS)

AF:

0.000840

AC:

AN:

3570

South Asian (SAS)

AF:

0.00

AC:

AN:

2687

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6019

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53175

Other (OTH)

AF:

0.00

AC:

AN:

1500

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000656

Hom.:

Bravo

AF:

0.000189

ESP6500AA

AF:

0.00156

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000988

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.076

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.026

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.33

MutationAssessor

Benign

1.2

PhyloP100

4.8

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-2.0

REVEL

Benign

0.24

Sift

Benign

0.075

Sift4G

Benign

0.29

Polyphen

1.0

Vest4

0.49

MVP

0.82

MPC

0.092

ClinPred

0.046

GERP RS

4.7

Varity_R

0.43

gMVP

0.49

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over