7-95486008-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016116.3(ASB4):​c.37G>A​(p.Ala13Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000973 in 1,614,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000099 ( 0 hom. )

Consequence

ASB4
NM_016116.3 missense

Scores

3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.956
Variant links:
Genes affected
ASB4 (HGNC:16009): (ankyrin repeat and SOCS box containing 4) 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. Multiple alternatively spliced transcript variants have been described for this gene but some of the full length sequences are not known. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1488744).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ASB4NM_016116.3 linkuse as main transcriptc.37G>A p.Ala13Thr missense_variant 1/5 ENST00000325885.6
ASB4NM_145872.3 linkuse as main transcriptc.37G>A p.Ala13Thr missense_variant 1/3
ASB4XM_017012303.2 linkuse as main transcriptc.37G>A p.Ala13Thr missense_variant 1/5
ASB4XM_047420471.1 linkuse as main transcriptc.8-9750G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ASB4ENST00000325885.6 linkuse as main transcriptc.37G>A p.Ala13Thr missense_variant 1/51 NM_016116.3 P1Q9Y574-1
ASB4ENST00000428113.5 linkuse as main transcriptc.37G>A p.Ala13Thr missense_variant 1/31 Q9Y574-2
ASB4ENST00000257621.4 linkuse as main transcriptn.157+7408G>A intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152182
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.000162
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000438
AC:
11
AN:
251278
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135818
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000704
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000992
AC:
145
AN:
1461778
Hom.:
0
Cov.:
30
AF XY:
0.000102
AC XY:
74
AN XY:
727200
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000119
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152300
Hom.:
0
Cov.:
32
AF XY:
0.0000671
AC XY:
5
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.000162
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000113
Hom.:
0
Bravo
AF:
0.0000718
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 08, 2024The c.37G>A (p.A13T) alteration is located in exon 1 (coding exon 1) of the ASB4 gene. This alteration results from a G to A substitution at nucleotide position 37, causing the alanine (A) at amino acid position 13 to be replaced by a threonine (T). 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
0.069
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
18
DANN
Uncertain
0.99
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.30
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.64
T;T
M_CAP
Benign
0.0077
T
MetaRNN
Benign
0.15
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L;L
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-0.65
N;N
REVEL
Benign
0.14
Sift
Benign
0.085
T;T
Sift4G
Uncertain
0.017
D;T
Polyphen
0.068
.;B
Vest4
0.34
MVP
0.55
MPC
0.057
ClinPred
0.047
T
GERP RS
3.3
Varity_R
0.059
gMVP
0.67

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: rs373298545; hg19: chr7-95115320; API