Genetic Variant ASB10:p.Arg434Cys (chr7-151176216-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PP3_ModerateBS2_Supporting

The NM_001142459.2(ASB10):c.1300C>T(p.Arg434Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000641 in 1,607,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

ASB10
NM_001142459.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.14

Publications

3 publications found

Variant links:

Genes affected

ASB10 (HGNC:17185): (ankyrin repeat and SOCS box containing 10) The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. The SOCS box serves to couple suppressor of cytokine signaling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Dec 2008]

ASB10 Gene-Disease associations (from GenCC):

glaucoma 1, open angle, F
Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ASB10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.882

BS2

High AC in GnomAd4 at 32 AD,Unknown gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142459.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASB10	NM_001142459.2	MANE Select	c.1300C>T	p.Arg434Cys	missense	Exon 5 of 6	NP_001135931.2	Q8WXI3-1
ASB10	NM_080871.4		c.1255C>T	p.Arg419Cys	missense	Exon 5 of 6	NP_543147.2	Q8WXI3-3
ASB10	NM_001142460.1		c.1186C>T	p.Arg396Cys	missense	Exon 4 of 5	NP_001135932.2	Q8WXI3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASB10	ENST00000420175.3	TSL:1 MANE Select	c.1300C>T	p.Arg434Cys	missense	Exon 5 of 6	ENSP00000391137.2	Q8WXI3-1
ASB10	ENST00000275838.5	TSL:1	c.1186C>T	p.Arg396Cys	missense	Exon 4 of 5	ENSP00000275838.1	Q8WXI3-2
ASB10	ENST00000968508.1		c.1300C>T	p.Arg434Cys	missense	Exon 5 of 6	ENSP00000638567.1

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000704

AC:

AN:

241522

AF XY:

0.0000758

show subpopulations

Gnomad AFR exome

AF:

0.000453

Gnomad AMR exome

AF:

0.0000297

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000834

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000488

AC:

AN:

1455290

Hom.:

Cov.:

AF XY:

0.0000511

AC XY:

AN XY:

723926

show subpopulations

African (AFR)

AF:

0.000391

AC:

AN:

33258

American (AMR)

AF:

0.00

AC:

AN:

43854

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25756

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39634

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85672

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52066

Middle Eastern (MID)

AF:

0.000195

AC:

AN:

5130

European-Non Finnish (NFE)

AF:

0.0000423

AC:

AN:

1109802

Other (OTH)

AF:

0.000133

AC:

AN:

60118

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000210

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.000555

AC:

AN:

41440

American (AMR)

AF:

0.0000655

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

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:

0.000296

Hom.:

Bravo

AF:

0.000230

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000661

AC:

ClinVar

ClinVar submissions as Germline

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

0.32

BayesDel_addAF

Uncertain

0.081

BayesDel_noAF

Pathogenic

0.25

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.31

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.91

M_CAP

Uncertain

0.25

MetaRNN

Pathogenic

0.88

MetaSVM

Uncertain

-0.0053

MutationAssessor

Pathogenic

3.8

PhyloP100

2.1

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-7.2

REVEL

Uncertain

0.58

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.91

MVP

0.66

MPC

0.37

ClinPred

0.97

GERP RS

4.7

Varity_R

0.85

gMVP

0.74

Mutation Taster

=40/60

disease causing

(source)

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

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