Genetic Variant NM_001142459.2:c.1078C>G (chr7-151180965-G-C) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001142459.2(ASB10):c.1078C>G(p.Arg360Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,413,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R360H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ASB10
NM_001142459.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.32

Publications

7 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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.927

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
ASB10	NM_001142459.2	MANE Select	c.1078C>G	p.Arg360Gly	missense	Exon 3 of 6	NP_001135931.2
ASB10	NM_080871.4		c.1033C>G	p.Arg345Gly	missense	Exon 3 of 6	NP_543147.2
ASB10	NM_001142460.1		c.1078C>G	p.Arg360Gly	missense	Exon 3 of 5	NP_001135932.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ASB10	ENST00000420175.3	TSL:1 MANE Select	c.1078C>G	p.Arg360Gly	missense	Exon 3 of 6	ENSP00000391137.2
ASB10	ENST00000275838.5	TSL:1	c.1078C>G	p.Arg360Gly	missense	Exon 3 of 5	ENSP00000275838.1
ASB10	ENST00000377867.7	TSL:2	c.1033C>G	p.Arg345Gly	missense	Exon 3 of 6	ENSP00000367098.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000463

AC:

AN:

216124

AF XY:

0.00000838

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000142

AC:

AN:

1413422

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

696076

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32490

American (AMR)

AF:

0.00

AC:

AN:

40840

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24172

East Asian (EAS)

AF:

0.00

AC:

AN:

38702

South Asian (SAS)

AF:

0.0000243

AC:

AN:

82332

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4678

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1082598

Other (OTH)

AF:

0.00

AC:

AN:

57980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.66

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Pathogenic

0.20

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.093

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.88

M_CAP

Uncertain

0.14

MetaRNN

Pathogenic

0.93

MetaSVM

Benign

-0.48

MutationAssessor

Pathogenic

3.0

PhyloP100

2.3

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-4.3

REVEL

Uncertain

0.51

Sift

Uncertain

0.029

Sift4G

Uncertain

0.021

Polyphen

1.0

Vest4

0.82

MVP

0.68

MPC

0.25

ClinPred

0.99

GERP RS

2.0

Varity_R

0.36

gMVP

0.69

Mutation Taster

=28/72

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over