Genetic Variant ASB12:p.Arg285His (chrX-64224438-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_130388.4(ASB12):c.854G>A(p.Arg285His) variant causes a missense change. The variant allele was found at a frequency of 0.00000827 in 1,208,502 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts 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. R285C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000073 ( 0 hom. 2 hem. )

Consequence

ASB12
NM_130388.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.59

Publications

2 publications found

Variant links:

Genes affected

ASB12 (HGNC:19763): (ankyrin repeat and SOCS box containing 12) 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 a 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. [provided by RefSeq, Jan 2011]

ASB12 links:

LOC112268307 (HGNC:):

LOC112268307 links:

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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=0.2576068).

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130388.4. 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
	ASB12	NM_130388.4	MANE Select	c.854G>A	p.Arg285His	missense	Exon 3 of 3	NP_569059.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASB12	ENST00000362002.3	TSL:2 MANE Select	c.854G>A	p.Arg285His	missense	Exon 3 of 3	ENSP00000355195.2	Q8WXK4-2
ENSG00000287370	ENST00000671386.1		n.171-8953C>T		intron	N/A
ENSG00000287370	ENST00000747759.1		n.229+17398C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

111273

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:

0.0000377

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000274

AC:

AN:

182242

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000764

Gnomad AMR exome

AF:

0.0000366

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000729

AC:

AN:

1097229

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

362611

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26384

American (AMR)

AF:

0.0000284

AC:

AN:

35180

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19369

East Asian (EAS)

AF:

0.00

AC:

AN:

30190

South Asian (SAS)

AF:

0.0000740

AC:

AN:

54050

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40489

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4131

European-Non Finnish (NFE)

AF:

0.00000357

AC:

AN:

841375

Other (OTH)

AF:

0.00

AC:

AN:

46061

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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:

0.0000180

AC:

AN:

111273

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33483

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30504

American (AMR)

AF:

0.00

AC:

AN:

10545

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2639

East Asian (EAS)

AF:

0.00

AC:

AN:

3520

South Asian (SAS)

AF:

0.00

AC:

AN:

2602

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6004

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000377

AC:

AN:

53036

Other (OTH)

AF:

0.00

AC:

AN:

1498

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000712

Hom.:

Bravo

AF:

0.0000416

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

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

0.24

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

(source)

DANN

Uncertain

1.0

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.054

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.59

PhyloP100

4.6

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.29

MVP

0.52

MPC

0.014

ClinPred

0.68

GERP RS

1.9

gMVP

0.83

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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