Variant 7-123616429-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001290258.2(ASB15):c.226G>A(p.Gly76Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00037 in 1,609,148 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00037 ( 0 hom. )

Consequence

ASB15
NM_001290258.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.41

Variant links:

Genes affected

ASB15 (HGNC:19767): (ankyrin repeat and SOCS box containing 15) This gene encodes a member of the suppressor of cytokine signaling box superfamily. The proteins in this superfamily participate in the ubiquitin-proteasome system for the degradation of proteins in the cell cycle and signal transduction pathways. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ASB15 links:

ASB15-AS1 (HGNC:):

ASB15-AS1 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
ASB15	NM_001290258.2 linkuse as main transcript	c.226G>A	p.Gly76Arg	missense_variant	6/12	ENST00000451215.6	NP_001277187.1	Q8WXK1A0A384NYV2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASB15	ENST00000451215.6 linkuse as main transcript	c.226G>A	p.Gly76Arg	missense_variant	6/12	2	NM_001290258.2	ENSP00000416433.1		Q8WXK1

Frequencies

GnomAD3 genomes

AF:

0.000349

AC:

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000618

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000227

AC:

AN:

250872

Hom.:

AF XY:

0.000236

AC XY:

AN XY:

135606

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000870

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000467

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000373

AC:

543

AN:

1457108

Hom.:

Cov.:

AF XY:

0.000354

AC XY:

257

AN XY:

725100

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000896

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000468

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000349

AC:

AN:

152040

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000618

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000476

Hom.:

Bravo

AF:

0.000291

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000222

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000356

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

Sep 17, 2021

The c.226G>A (p.G76R) alteration is located in exon 4 (coding exon 3) of the ASB15 gene. This alteration results from a G to A substitution at nucleotide position 226, causing the glycine (G) at amino acid position 76 to be replaced by an arginine (R). 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

Pathogenic

0.68

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.052

T;T;.;T;.;T

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.91

.;.;D;.;D;D

M_CAP

Uncertain

0.23

MetaRNN

Uncertain

0.70

D;D;D;D;D;D

MetaSVM

Uncertain

0.69

MutationAssessor

Pathogenic

3.1

M;M;.;M;.;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.64

PROVEAN

Pathogenic

-6.4

D;D;D;D;D;D

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

D;D;D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D;D;D

Polyphen

1.0

D;D;.;D;.;D

Vest4

0.59

MutPred

0.87

Loss of ubiquitination at K75 (P = 0.0665);Loss of ubiquitination at K75 (P = 0.0665);Loss of ubiquitination at K75 (P = 0.0665);Loss of ubiquitination at K75 (P = 0.0665);Loss of ubiquitination at K75 (P = 0.0665);Loss of ubiquitination at K75 (P = 0.0665);

MVP

0.87

MPC

0.67

ClinPred

0.91

GERP RS

5.1

Varity_R

0.86

gMVP

0.81

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

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