chr9-129637905-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_017873.4(ASB6):​c.1151G>A​(p.Arg384Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000127 in 1,580,740 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R384W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

ASB6
NM_017873.4 missense

Scores

7
8
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.15
Variant links:
Genes affected
ASB6 (HGNC:17181): (ankyrin repeat and SOCS box containing 6) The protein encoded by this gene belongs to a family of ankyrin repeat proteins that, along with four other protein families, contain a C-terminal SOCS box motif. Growing evidence suggests that the SOCS box, similar to the F-box, acts as a bridge between specific substrate-binding domains and the more generic proteins that comprise a large family of E3 ubiquitin protein ligases. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Jan 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ASB6NM_017873.4 linkc.1151G>A p.Arg384Gln missense_variant Exon 6 of 6 ENST00000277458.5 NP_060343.1 Q9NWX5-1
ASB6NM_001202403.2 linkc.1064G>A p.Arg355Gln missense_variant Exon 5 of 5 NP_001189332.1 Q9NWX5F6TX30
ASB6NM_177999.3 linkc.*448G>A 3_prime_UTR_variant Exon 5 of 5 NP_821066.1 Q9NWX5-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ASB6ENST00000277458.5 linkc.1151G>A p.Arg384Gln missense_variant Exon 6 of 6 1 NM_017873.4 ENSP00000277458.4 Q9NWX5-1
ASB6ENST00000450050.6 linkc.1064G>A p.Arg355Gln missense_variant Exon 5 of 5 1 ENSP00000416172.3 F6TX30
ASB6ENST00000277459 linkc.*448G>A 3_prime_UTR_variant Exon 5 of 5 1 ENSP00000277459.4 Q9NWX5-2

Frequencies

GnomAD3 genomes
AF:
0.0000788
AC:
12
AN:
152206
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.000132
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000404
AC:
9
AN:
222700
Hom.:
0
AF XY:
0.0000418
AC XY:
5
AN XY:
119590
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000325
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000807
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000596
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000132
AC:
188
AN:
1428416
Hom.:
0
Cov.:
30
AF XY:
0.000126
AC XY:
89
AN XY:
707200
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000245
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000496
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000161
Gnomad4 OTH exome
AF:
0.000119
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152324
Hom.:
0
Cov.:
33
AF XY:
0.0000940
AC XY:
7
AN XY:
74466
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.0000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000904
Hom.:
0
Bravo
AF:
0.0000567
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000330
AC:
4

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 25, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1151G>A (p.R384Q) alteration is located in exon 6 (coding exon 6) of the ASB6 gene. This alteration results from a G to A substitution at nucleotide position 1151, causing the arginine (R) at amino acid position 384 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
0.42
BayesDel_addAF
Uncertain
0.087
D
BayesDel_noAF
Uncertain
0.080
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.19
T;T
Eigen
Pathogenic
0.72
Eigen_PC
Pathogenic
0.70
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
D;D
M_CAP
Benign
0.079
D
MetaRNN
Uncertain
0.69
D;D
MetaSVM
Uncertain
-0.23
T
MutationAssessor
Pathogenic
3.3
.;M
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-1.0
.;N
REVEL
Uncertain
0.39
Sift
Pathogenic
0.0
.;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
.;D
Vest4
0.82
MVP
0.72
MPC
1.2
ClinPred
0.93
D
GERP RS
5.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.51
gMVP
0.77

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: rs199686158; hg19: chr9-132400184; API