dbSNP rs201303910: ASB12:p.Ala189Ser (chrX-64225086-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

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

The NM_130388.4(ASB12):c.565G>T(p.Ala189Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000165 in 1,209,626 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 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. A189T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

ASB12
NM_130388.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.09

Variant links:

Genes affected

ASB12 (HGNC:19763): (ankyrin repeat and SOCS box containing 12) 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 a 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. [provided by RefSeq, Jan 2011]

ASB12 links:

LOC112268307 (HGNC:):

LOC112268307 links:

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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, 0.779

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASB12	NM_130388.4 link	c.565G>T	p.Ala189Ser	missense_variant	Exon 2 of 3	ENST00000362002.3	NP_569059.3	Q8WXK4-2
LOC112268307	XM_047442705.1 link	c.125+18046C>A		intron_variant	Intron 2 of 4		XP_047298661.1
LOC112268307	XM_047442706.1 link	c.125+18046C>A		intron_variant	Intron 2 of 3		XP_047298662.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASB12	ENST00000362002.3 link	c.565G>T	p.Ala189Ser	missense_variant	Exon 2 of 3	2	NM_130388.4	ENSP00000355195.2		Q8WXK4-2
ENSG00000287370	ENST00000671386.1 link	n.171-8305C>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.00000896

AC:

AN:

111567

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

33747

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1098059

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363413

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000896

AC:

AN:

111567

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

33747

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:

0.0000188

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.027

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Uncertain

1.0

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.023

MetaRNN

Pathogenic

0.78

MetaSVM

Benign

-0.58

PROVEAN

Benign

-2.4

REVEL

Uncertain

0.35

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.036

Vest4

0.71

MVP

0.62

MPC

0.053

ClinPred

0.97

GERP RS

4.0

gMVP

0.63

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over