X-64224438-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_130388.4(ASB12):​c.854G>A​(p.Arg285His) variant causes a missense change. The variant allele was found at a frequency of 0.00000827 in 1,208,502 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R285C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 22)
Exomes 𝑓: 0.0000073 ( 0 hom. 2 hem. )

Consequence

ASB12
NM_130388.4 missense

Scores

2
6
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.59
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.2576068).
BS2
High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ASB12NM_130388.4 linkc.854G>A p.Arg285His missense_variant Exon 3 of 3 ENST00000362002.3 NP_569059.3 Q8WXK4-2
LOC112268307XM_047442705.1 linkc.125+17398C>T intron_variant Intron 2 of 4 XP_047298661.1
LOC112268307XM_047442706.1 linkc.125+17398C>T intron_variant Intron 2 of 3 XP_047298662.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ASB12ENST00000362002.3 linkc.854G>A p.Arg285His missense_variant Exon 3 of 3 2 NM_130388.4 ENSP00000355195.2 Q8WXK4-2
ENSG00000287370ENST00000671386.1 linkn.171-8953C>T intron_variant Intron 2 of 2

Frequencies

GnomAD3 genomes
AF:
0.0000180
AC:
2
AN:
111273
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
33483
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:
0.0000377
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000274
AC:
5
AN:
182242
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
66792
show subpopulations
Gnomad AFR exome
AF:
0.0000764
Gnomad AMR exome
AF:
0.0000366
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000159
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000729
AC:
8
AN:
1097229
Hom.:
0
Cov.:
30
AF XY:
0.00000552
AC XY:
2
AN XY:
362611
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000284
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000740
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000357
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000180
AC:
2
AN:
111273
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
33483
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:
0.0000377
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000416
ESP6500AA
AF:
0.000261
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 20, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.854G>A (p.R285H) alteration is located in exon 3 (coding exon 2) of the ASB12 gene. This alteration results from a G to A substitution at nucleotide position 854, causing the arginine (R) at amino acid position 285 to be replaced by a histidine (H). 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
BayesDel_addAF
Benign
-0.059
T
BayesDel_noAF
Uncertain
-0.060
CADD
Uncertain
23
DANN
Uncertain
1.0
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.054
D
MetaRNN
Benign
0.26
T
MetaSVM
Benign
-0.59
T
PROVEAN
Uncertain
-3.9
D
REVEL
Uncertain
0.47
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Vest4
0.29
MVP
0.52
MPC
0.014
ClinPred
0.68
D
GERP RS
1.9
gMVP
0.83

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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.

Other links and lift over

dbSNP: rs144858124; hg19: chrX-63444318; COSMIC: COSV100744798; API