dbSNP rs368512399: ASB11:p.Gly197Arg (chrX-15289570-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_080873.3(ASB11):c.589G>A(p.Gly197Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000128 in 1,206,728 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 47 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000090 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.00013 ( 0 hom. 45 hem. )

Consequence

ASB11
NM_080873.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.75

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 -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.859

BS2

High Hemizygotes in GnomAd4 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASB11	NM_080873.3	MANE Select	c.589G>A	p.Gly197Arg	missense	Exon 5 of 7	NP_543149.1	Q8WXH4-1
ASB11	NM_001201583.2		c.538G>A	p.Gly180Arg	missense	Exon 5 of 7	NP_001188512.1	Q8WXH4-2
ASB11	NM_001012428.2		c.526G>A	p.Gly176Arg	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.589G>A	p.Gly197Arg	missense	Exon 5 of 7	ENSP00000417914.1	Q8WXH4-1
ASB11	ENST00000380470.7	TSL:1	c.538G>A	p.Gly180Arg	missense	Exon 5 of 7	ENSP00000369837.3	Q8WXH4-2
ASB11	ENST00000485437.2	TSL:1	n.*32G>A		non_coding_transcript_exon	Exon 6 of 8	ENSP00000419385.2	F8WF31

Frequencies

GnomAD3 genomes

AF:

0.0000896

AC:

AN:

111596

Hom.:

Cov.:

show subpopulations

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:

0.000169

Gnomad OTH

AF:

0.000666

GnomAD2 exomes

AF:

0.0000491

AC:

AN:

183272

AF XY:

0.0000591

show subpopulations

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:

0.000110

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000132

AC:

145

AN:

1095132

Hom.:

Cov.:

AF XY:

0.000125

AC XY:

AN XY:

360592

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26338

American (AMR)

AF:

0.00

AC:

AN:

35191

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19360

East Asian (EAS)

AF:

0.00

AC:

AN:

30165

South Asian (SAS)

AF:

0.0000555

AC:

AN:

54060

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40520

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4128

European-Non Finnish (NFE)

AF:

0.000166

AC:

139

AN:

839382

Other (OTH)

AF:

0.0000652

AC:

AN:

45988

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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:

0.0000896

AC:

AN:

111596

Hom.:

Cov.:

AF XY:

0.0000592

AC XY:

AN XY:

33784

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30664

American (AMR)

AF:

0.00

AC:

AN:

10476

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2644

East Asian (EAS)

AF:

0.00

AC:

AN:

3569

South Asian (SAS)

AF:

0.00

AC:

AN:

2672

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6008

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.000169

AC:

AN:

53140

Other (OTH)

AF:

0.000666

AC:

AN:

1501

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

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:

0.000174

Hom.:

Bravo

AF:

0.0000756

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

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

Pathogenic

0.84

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Pathogenic

0.21

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.080

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.98

M_CAP

Uncertain

0.19

MetaRNN

Pathogenic

0.86

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.91

PhyloP100

6.7

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-7.8

REVEL

Uncertain

0.51

Sift

Pathogenic

0.0

Sift4G

Benign

0.064

Polyphen

1.0

Vest4

0.88

MutPred

0.48

Gain of catalytic residue at G197 (P = 0.052)

MVP

0.76

MPC

0.30

ClinPred

0.60

GERP RS

5.6

Varity_R

0.95

gMVP

0.83

Mutation Taster

=91/9

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