chrX-64224365-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_130388.4(ASB12):​c.927G>A​(p.Met309Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,209,151 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 30 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00066 ( 0 hom., 18 hem., cov: 23)
Exomes 𝑓: 0.000052 ( 0 hom. 12 hem. )

Consequence

ASB12
NM_130388.4 missense

Scores

13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0150
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.017632037).
BS2
High Hemizygotes in GnomAd4 at 18 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ASB12NM_130388.4 linkc.927G>A p.Met309Ile missense_variant Exon 3 of 3 ENST00000362002.3 NP_569059.3 Q8WXK4-2
LOC112268307XM_047442705.1 linkc.125+17325C>T intron_variant Intron 2 of 4 XP_047298661.1
LOC112268307XM_047442706.1 linkc.125+17325C>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.927G>A p.Met309Ile missense_variant Exon 3 of 3 2 NM_130388.4 ENSP00000355195.2 Q8WXK4-2
ENSG00000287370ENST00000671386.1 linkn.171-9026C>T intron_variant Intron 2 of 2

Frequencies

GnomAD3 genomes
AF:
0.000664
AC:
74
AN:
111382
Hom.:
0
Cov.:
23
AF XY:
0.000536
AC XY:
18
AN XY:
33570
show subpopulations
Gnomad AFR
AF:
0.00235
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000953
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:
0.00
Gnomad OTH
AF:
0.000665
GnomAD3 exomes
AF:
0.000114
AC:
21
AN:
183412
Hom.:
0
AF XY:
0.0000737
AC XY:
5
AN XY:
67852
show subpopulations
Gnomad AFR exome
AF:
0.00152
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:
0.00
Gnomad OTH exome
AF:
0.000221
GnomAD4 exome
AF:
0.0000519
AC:
57
AN:
1097715
Hom.:
0
Cov.:
30
AF XY:
0.0000331
AC XY:
12
AN XY:
363079
show subpopulations
Gnomad4 AFR exome
AF:
0.00174
Gnomad4 AMR exome
AF:
0.0000852
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:
0.000152
GnomAD4 genome
AF:
0.000664
AC:
74
AN:
111436
Hom.:
0
Cov.:
23
AF XY:
0.000535
AC XY:
18
AN XY:
33634
show subpopulations
Gnomad4 AFR
AF:
0.00235
Gnomad4 AMR
AF:
0.0000951
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000656
Alfa
AF:
0.0000706
Hom.:
2
Bravo
AF:
0.000842
ESP6500AA
AF:
0.00209
AC:
8
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000132
AC:
16

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Mar 06, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.927G>A (p.M309I) 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 927, causing the methionine (M) at amino acid position 309 to be replaced by an isoleucine (I). 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
-0.75
T
BayesDel_noAF
Benign
-0.86
CADD
Benign
7.6
DANN
Benign
0.90
FATHMM_MKL
Benign
0.035
N
LIST_S2
Benign
0.72
T
M_CAP
Benign
0.0024
T
MetaRNN
Benign
0.018
T
MetaSVM
Benign
-1.0
T
PROVEAN
Benign
-0.34
N
REVEL
Benign
0.070
Sift
Benign
0.45
T
Sift4G
Benign
0.24
T
Vest4
0.14
MVP
0.64
MPC
0.0088
ClinPred
0.011
T
GERP RS
1.1
gMVP
0.20

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.

Other links and lift over

dbSNP: rs139928365; hg19: chrX-63444245; API