Variant chrX-15250519-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000380488.9(ASB9):c.479T>C(p.Ile160Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000639 in 1,096,015 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000064 ( 0 hom. 1 hem. )

Consequence

ASB9
ENST00000380488.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.79

Variant links:

Genes affected

ASB9 (HGNC:17184): (ankyrin repeat and SOCS box containing 9) This gene encodes a member of the ankyrin repeat and suppressor of cytokine signaling (SOCS) box protein family. Members of this family can interact with the elongin B-C adapter complex via their SOCS box domain and further complex with the cullin and ring box proteins to form E3 ubiquitin ligase complexes. They may function to mediate the substrate-recognition of the E3 ubiquitin ligases. A transcribed pseudogene of this gene has been identified on chromosome 15. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

ASB9 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASB9	NM_001031739.3 linkuse as main transcript	c.479T>C	p.Ile160Thr	missense_variant	5/7	ENST00000380488.9	NP_001026909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASB9	ENST00000380488.9 linkuse as main transcript	c.479T>C	p.Ile160Thr	missense_variant	5/7	1	NM_001031739.3	ENSP00000369855	P1	Q96DX5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000109

AC:

AN:

183407

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

67841

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 SAS exome

AF:

0.0000524

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000639

AC:

AN:

1096015

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

361487

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000714

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000548

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 02, 2024

The c.479T>C (p.I160T) alteration is located in exon 5 (coding exon 5) of the ASB9 gene. This alteration results from a T to C substitution at nucleotide position 479, causing the isoleucine (I) at amino acid position 160 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

.;.;T;.

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.52

T;.;T;T

M_CAP

Pathogenic

0.34

MetaRNN

Uncertain

0.62

D;D;D;D

MetaSVM

Benign

-0.73

MutationAssessor

Benign

1.8

.;L;L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.6

D;D;D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.0060

D;D;D;D

Sift4G

Uncertain

0.0090

D;D;D;D

Polyphen

0.99, 0.97

.;D;D;D

Vest4

0.43

MutPred

0.59

.;Gain of disorder (P = 0.0314);Gain of disorder (P = 0.0314);Gain of disorder (P = 0.0314);

MVP

0.69

MPC

0.79

ClinPred

0.80

GERP RS

5.8

Varity_R

0.53

gMVP

0.59

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over