Genetic Variant ASB10:p.Arg189Gly (chr7-151186411-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001142459.2(ASB10):c.565C>G(p.Arg189Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,435,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R189W) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

ASB10
NM_001142459.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.228

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10077694).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ASB10	NM_001142459.2 link	c.565C>G	p.Arg189Gly	missense_variant	Exon 2 of 6	ENST00000420175.3	NP_001135931.2
ASB10	NM_080871.4 link	c.520C>G	p.Arg174Gly	missense_variant	Exon 2 of 6		NP_543147.2
ASB10	NM_001142460.1 link	c.565C>G	p.Arg189Gly	missense_variant	Exon 2 of 5		NP_001135932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ASB10	ENST00000420175.3 link	c.565C>G	p.Arg189Gly	missense_variant	Exon 2 of 6	1	NM_001142459.2	ENSP00000391137.2
ASB10	ENST00000275838.5 link	c.565C>G	p.Arg189Gly	missense_variant	Exon 2 of 5	1		ENSP00000275838.1
ASB10	ENST00000377867.7 link	c.520C>G	p.Arg174Gly	missense_variant	Exon 2 of 6	2		ENSP00000367098.3
ASB10	ENST00000415615.1 link	n.*609C>G		downstream_gene_variant		4		ENSP00000410871.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.97e-7

AC:

AN:

1435050

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

711338

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

32930

American (AMR)

AF:

0.00

AC:

AN:

40834

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25544

East Asian (EAS)

AF:

0.00

AC:

AN:

38240

South Asian (SAS)

AF:

0.00

AC:

AN:

82284

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51210

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5480

European-Non Finnish (NFE)

AF:

9.10e-7

AC:

AN:

1099174

Other (OTH)

AF:

0.00

AC:

AN:

59354

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.083

.;.;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.067

LIST_S2

Benign

0.60

T;T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.10

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.15

N;.;N

PhyloP100

0.23

PrimateAI

Benign

0.26

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.15

Sift

Benign

0.11

T;T;T

Sift4G

Benign

0.31

T;T;T

Polyphen

0.0, 0.0010

.;B;B

Vest4

0.19

MVP

0.57

MPC

0.059

ClinPred

0.061

GERP RS

0.86

Varity_R

0.098

gMVP

0.30

Mutation Taster

=98/2

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over