Genetic Variant ASB5:p.Arg302Gln (chr4-176215685-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_080874.4(ASB5):c.905G>A(p.Arg302Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,460,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

ASB5
NM_080874.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.74

Variant links:

Genes affected

ASB5 (HGNC:17180): (ankyrin repeat and SOCS box containing 5) The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. They contain ankyrin repeat sequence and SOCS box domain. The SOCS box serves to couple suppressor of cytokine signalling (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 but their full length sequences are not known. [provided by RefSeq, Jul 2008]

ASB5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.825

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB5	NM_080874.4 link	c.905G>A	p.Arg302Gln	missense_variant	Exon 7 of 7	ENST00000296525.7	NP_543150.1	Q8WWX0-1Q5HYF3
ASB5	NM_001410863.1 link	c.770G>A	p.Arg257Gln	missense_variant	Exon 7 of 7		NP_001397792.1
ASB5	XM_005262759.2 link	c.905G>A	p.Arg302Gln	missense_variant	Exon 9 of 9		XP_005262816.1	Q8WWX0-1Q5HYF3
ASB5	XM_011531617.4 link	c.746G>A	p.Arg249Gln	missense_variant	Exon 7 of 7		XP_011529919.1	Q8WWX0-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ASB5	ENST00000296525.7 link	c.905G>A	p.Arg302Gln	missense_variant	Exon 7 of 7	1	NM_080874.4	ENSP00000296525.3	Q8WWX0-1
ASB5	ENST00000672074.1 link	c.770G>A	p.Arg257Gln	missense_variant	Exon 7 of 7			ENSP00000500617.1	A0A5F9ZHS2
ASB5	ENST00000512254.1 link	c.746G>A	p.Arg249Gln	missense_variant	Exon 7 of 7	2		ENSP00000422877.1	Q8WWX0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250698

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135568

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000103

AC:

AN:

1460492

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726622

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000177

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000548

EpiControl

AF:

0.0000594

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 19, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.905G>A (p.R302Q) alteration is located in exon 7 (coding exon 7) of the ASB5 gene. This alteration results from a G to A substitution at nucleotide position 905, causing the arginine (R) at amino acid position 302 to be replaced by a glutamine (Q). 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

Uncertain

0.36

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Pathogenic

0.19

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.19

T;.

Eigen

Pathogenic

0.80

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Benign

0.080

MetaRNN

Pathogenic

0.83

D;D

MetaSVM

Uncertain

0.089

MutationAssessor

Pathogenic

3.4

M;.

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.6

D;D

REVEL

Uncertain

0.44

Sift

Benign

0.035

D;D

Sift4G

Uncertain

0.039

D;D

Polyphen

1.0

D;.

Vest4

0.80

MVP

0.78

MPC

0.39

ClinPred

0.97

GERP RS

5.3

Varity_R

0.59

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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