Genetic Variant NM_080873.3:c.767G>A (chrX-15287961-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.767G>A(p.Arg256His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,210,640 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 57 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 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. R256L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., 10 hem., cov: 24)

Exomes 𝑓: 0.00010 ( 0 hom. 47 hem. )

Consequence

ASB11
NM_080873.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.560

Publications

4 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=0.0777553).

BS2

High Hemizygotes in GnomAd4 at 10 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.767G>A	p.Arg256His	missense	Exon 6 of 7	NP_543149.1	Q8WXH4-1
ASB11	NM_001201583.2		c.716G>A	p.Arg239His	missense	Exon 6 of 7	NP_001188512.1	Q8WXH4-2
ASB11	NM_001012428.2		c.704G>A	p.Arg235His	missense	Exon 6 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.767G>A	p.Arg256His	missense	Exon 6 of 7	ENSP00000417914.1	Q8WXH4-1
ASB11	ENST00000380470.7	TSL:1	c.716G>A	p.Arg239His	missense	Exon 6 of 7	ENSP00000369837.3	Q8WXH4-2
ASB11	ENST00000485437.2	TSL:1	n.*210G>A		non_coding_transcript_exon	Exon 7 of 8	ENSP00000419385.2	F8WF31

Frequencies

GnomAD3 genomes

AF:

0.000160

AC:

AN:

112567

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000281

Gnomad SAS

AF:

0.000363

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000375

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000153

AC:

AN:

183014

AF XY:

0.000178

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000769

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000724

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000734

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000103

AC:

113

AN:

1098073

Hom.:

Cov.:

AF XY:

0.000129

AC XY:

AN XY:

363431

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26400

American (AMR)

AF:

0.000511

AC:

AN:

35198

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19380

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30198

South Asian (SAS)

AF:

0.0000185

AC:

AN:

54109

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40529

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4135

European-Non Finnish (NFE)

AF:

0.000106

AC:

AN:

842037

Other (OTH)

AF:

0.0000868

AC:

AN:

46087

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

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:

0.000160

AC:

AN:

112567

Hom.:

Cov.:

AF XY:

0.000288

AC XY:

AN XY:

34735

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30985

American (AMR)

AF:

0.00132

AC:

AN:

10622

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2655

East Asian (EAS)

AF:

0.000281

AC:

AN:

3565

South Asian (SAS)

AF:

0.000363

AC:

AN:

2753

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6187

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.0000375

AC:

AN:

53362

Other (OTH)

AF:

0.00

AC:

AN:

1512

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.0000261

Hom.:

Bravo

AF:

0.000257

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.73

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.32

M_CAP

Benign

0.037

MetaRNN

Benign

0.078

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

PhyloP100

0.56

PrimateAI

Benign

0.19

PROVEAN

Benign

-1.0

REVEL

Benign

0.035

Sift

Benign

0.096

Sift4G

Benign

0.29

Polyphen

0.40

Vest4

0.26

MutPred

0.38

Loss of MoRF binding (P = 0.0104)

MVP

0.94

MPC

0.057

ClinPred

0.028

GERP RS

1.2

Varity_R

0.19

gMVP

0.25

Mutation Taster

=94/6

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

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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