Genetic Variant ASB11:p.Tyr322Cys (chrX-15283512-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_080873.3(ASB11):c.965A>G(p.Tyr322Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000132 in 1,208,611 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000012 ( 0 hom. 5 hem. )

Consequence

ASB11
NM_080873.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.82

Variant links:

Genes affected

ASB11 (HGNC:17186): (ankyrin repeat and SOCS box containing 11) 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. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

ASB11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB11	NM_080873.3 link	c.965A>G	p.Tyr322Cys	missense_variant	Exon 7 of 7	ENST00000480796.6	NP_543149.1	Q8WXH4-1
ASB11	NM_001201583.2 link	c.914A>G	p.Tyr305Cys	missense_variant	Exon 7 of 7		NP_001188512.1	Q8WXH4-2
ASB11	NM_001012428.2 link	c.902A>G	p.Tyr301Cys	missense_variant	Exon 7 of 7		NP_001012428.1	Q8WXH4-3Q7Z670

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB11	ENST00000480796.6 link	c.965A>G	p.Tyr322Cys	missense_variant	Exon 7 of 7	1	NM_080873.3	ENSP00000417914.1		Q8WXH4-1

Frequencies

GnomAD3 genomes

AF:

0.0000270

AC:

AN:

111005

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33271

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000378

Gnomad OTH

AF:

0.000665

GnomAD3 exomes

AF:

0.0000218

AC:

AN:

183483

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

67913

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000488

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000118

AC:

AN:

1097606

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

362972

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000713

Gnomad4 OTH exome

AF:

0.000109

GnomAD4 genome

AF:

0.0000270

AC:

AN:

111005

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33271

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000378

Gnomad4 OTH

AF:

0.000665

Bravo

AF:

0.00000756

ExAC

AF:

0.0000412

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 01, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.965A>G (p.Y322C) alteration is located in exon 7 (coding exon 7) of the ASB11 gene. This alteration results from a A to G substitution at nucleotide position 965, causing the tyrosine (Y) at amino acid position 322 to be replaced by a cysteine (C). 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

0.19

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.31

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

.;.;T

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.71

T;T;T

M_CAP

Pathogenic

0.47

MetaRNN

Uncertain

0.52

D;D;D

MetaSVM

Uncertain

-0.070

MutationAssessor

Pathogenic

3.2

.;.;M

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-5.9

D;D;D

REVEL

Uncertain

0.42

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.024

D;D;D

Polyphen

1.0

.;.;D

Vest4

0.23

MutPred

0.63

.;.;Gain of disorder (P = 0.0808);

MVP

0.80

MPC

0.30

ClinPred

0.82

GERP RS

5.7

Varity_R

0.69

gMVP

0.54

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