Genetic Variant ASB10:p.Leu366Val (chr7-151180947-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001142459.2(ASB10):c.1096C>G(p.Leu366Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,258 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. L366F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

ASB10
NM_001142459.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.09

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
ASB10	NM_001142459.2 link	c.1096C>G	p.Leu366Val	missense_variant	Exon 3 of 6	ENST00000420175.3	NP_001135931.2
ASB10	NM_080871.4 link	c.1051C>G	p.Leu351Val	missense_variant	Exon 3 of 6		NP_543147.2
ASB10	NM_001142460.1 link	c.1096C>G	p.Leu366Val	missense_variant	Exon 3 of 5		NP_001135932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
ASB10	ENST00000420175.3 link	c.1096C>G	p.Leu366Val	missense_variant	Exon 3 of 6	1	NM_001142459.2	ENSP00000391137.2
ASB10	ENST00000275838.5 link	c.1096C>G	p.Leu366Val	missense_variant	Exon 3 of 5	1		ENSP00000275838.1
ASB10	ENST00000377867.7 link	c.1051C>G	p.Leu351Val	missense_variant	Exon 3 of 6	2		ENSP00000367098.3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41468

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68048

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Uncertain

0.047

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0

.;.;T

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.78

T;D;D

M_CAP

Uncertain

0.099

MetaRNN

Uncertain

0.59

D;D;D

MetaSVM

Benign

-0.38

MutationAssessor

Uncertain

2.3

M;.;M

PhyloP100

4.1

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.79

N;N;N

REVEL

Benign

0.26

Sift

Uncertain

0.014

D;D;D

Sift4G

Uncertain

0.021

D;D;D

Vest4

0.62

ClinPred

0.97

GERP RS

5.1

Varity_R

0.27

gMVP

0.43

Mutation Taster

=39/61

disease causing

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over