NM_001142459.2:c.1357C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001142459.2(ASB10):c.1357C>T(p.Arg453Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00967 in 1,611,814 control chromosomes in the GnomAD database, including 648 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R453H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.019 ( 94 hom., cov: 33)

Exomes 𝑓: 0.0087 ( 554 hom. )

Consequence

ASB10
NM_001142459.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.474

Publications

12 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: AD, Unknown Classification: LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ASB10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016953051).

BP6

Variant 7-151176159-G-A is Benign according to our data. Variant chr7-151176159-G-A is described in ClinVar as Benign. ClinVar VariationId is 1233189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB10	NM_001142459.2 link	c.1357C>T	p.Arg453Cys	missense_variant	Exon 5 of 6	ENST00000420175.3	NP_001135931.2	Q8WXI3-1
ASB10	NM_080871.4 link	c.1312C>T	p.Arg438Cys	missense_variant	Exon 5 of 6		NP_543147.2	Q8WXI3-3
ASB10	NM_001142460.1 link	c.1243C>T	p.Arg415Cys	missense_variant	Exon 4 of 5		NP_001135932.2	Q8WXI3-2A0A090N8I2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ASB10	ENST00000420175.3 link	c.1357C>T	p.Arg453Cys	missense_variant	Exon 5 of 6	1	NM_001142459.2	ENSP00000391137.2	Q8WXI3-1
ASB10	ENST00000275838.5 link	c.1243C>T	p.Arg415Cys	missense_variant	Exon 4 of 5	1		ENSP00000275838.1	Q8WXI3-2
ASB10	ENST00000377867.7 link	c.1312C>T	p.Arg438Cys	missense_variant	Exon 5 of 6	2		ENSP00000367098.3	Q8WXI3-3

Frequencies

GnomAD3 genomes

AF:

0.0188

AC:

2861

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0263

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0171

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.138

Gnomad SAS

AF:

0.0253

Gnomad FIN

AF:

0.0517

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00144

Gnomad OTH

AF:

0.0124

GnomAD2 exomes

AF:

0.0229

AC:

5630

AN:

245418

AF XY:

0.0213

show subpopulations

Gnomad AFR exome

AF:

0.0286

Gnomad AMR exome

AF:

0.0236

Gnomad ASJ exome

AF:

0.000303

Gnomad EAS exome

AF:

0.137

Gnomad FIN exome

AF:

0.0510

Gnomad NFE exome

AF:

0.00146

Gnomad OTH exome

AF:

0.0146

GnomAD4 exome

AF:

0.00872

AC:

12720

AN:

1459532

Hom.:

554

Cov.:

AF XY:

0.00884

AC XY:

6418

AN XY:

726082

show subpopulations

African (AFR)

AF:

0.0273

AC:

913

AN:

33450

American (AMR)

AF:

0.0213

AC:

953

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.0000766

AC:

AN:

26122

East Asian (EAS)

AF:

0.131

AC:

5216

AN:

39690

South Asian (SAS)

AF:

0.0188

AC:

1619

AN:

86196

European-Finnish (FIN)

AF:

0.0461

AC:

2408

AN:

52268

Middle Eastern (MID)

AF:

0.00398

AC:

AN:

5030

European-Non Finnish (NFE)

AF:

0.000662

AC:

736

AN:

1111800

Other (OTH)

AF:

0.0142

AC:

853

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

680

1360

2041

2721

3401

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

328

492

656

820

<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:

0.0189

AC:

2873

AN:

152282

Hom.:

Cov.:

AF XY:

0.0221

AC XY:

1646

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0264

AC:

1096

AN:

41568

American (AMR)

AF:

0.0170

AC:

260

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.139

AC:

717

AN:

5166

South Asian (SAS)

AF:

0.0261

AC:

126

AN:

4824

European-Finnish (FIN)

AF:

0.0517

AC:

548

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00144

AC:

AN:

68024

Other (OTH)

AF:

0.0132

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

146

291

437

582

728

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.00633

Hom.:

122

Bravo

AF:

0.0190

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.0233

AC:

102

ESP6500EA

AF:

0.00187

AC:

ExAC

AF:

0.0215

AC:

2599

Asia WGS

AF:

0.0810

AC:

284

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000652

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 31, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 26713451) -

Jan 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.014

.;.;T

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.084

T;T;T

MetaRNN

Benign

0.0017

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

.;.;L

PhyloP100

0.47

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.26

N;N;N

REVEL

Benign

0.055

Sift

Benign

0.12

T;T;T

Sift4G

Benign

0.10

T;T;T

Polyphen

0.0010, 0.0050

.;B;B

Vest4

0.15

MPC

0.063

ClinPred

0.0032

GERP RS

1.7

Varity_R

0.079

gMVP

0.59

Mutation Taster

=96/4

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over