2-236214532-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_212556.4(ASB18):​c.931C>T​(p.Leu311Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000231 in 1,427,484 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

ASB18
NM_212556.4 missense

Scores

2
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.689
Variant links:
Genes affected
ASB18 (HGNC:19770): (ankyrin repeat and SOCS box containing 18) 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, Feb 2017]
GBX2-AS1 (HGNC:55714): (GBX2 and ASB18 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.2882831).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ASB18NM_212556.4 linkuse as main transcriptc.931C>T p.Leu311Phe missense_variant 4/6 ENST00000409749.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ASB18ENST00000409749.8 linkuse as main transcriptc.931C>T p.Leu311Phe missense_variant 4/61 NM_212556.4 P1Q6ZVZ8-1
GBX2-AS1ENST00000415226.1 linkuse as main transcriptn.224-44975G>A intron_variant, non_coding_transcript_variant 4

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151692
Hom.:
0
Cov.:
32
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000251
AC:
32
AN:
1275792
Hom.:
0
Cov.:
31
AF XY:
0.0000288
AC XY:
18
AN XY:
625376
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000289
Gnomad4 OTH exome
AF:
0.0000190
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151692
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74096
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000151

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 GeneticsMay 30, 2024The c.931C>T (p.L311F) alteration is located in exon 4 (coding exon 4) of the ASB18 gene. This alteration results from a C to T substitution at nucleotide position 931, causing the leucine (L) at amino acid position 311 to be replaced by a phenylalanine (F). 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
0.20
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.080
.;T;.
Eigen
Benign
-0.63
Eigen_PC
Benign
-0.64
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.69
T;T;T
M_CAP
Pathogenic
0.40
D
MetaRNN
Benign
0.29
T;T;T
MetaSVM
Benign
-0.86
T
MutationAssessor
Benign
1.6
.;L;.
MutationTaster
Benign
0.97
N;N
PrimateAI
Pathogenic
0.90
D
PROVEAN
Uncertain
-2.7
.;D;D
REVEL
Benign
0.13
Sift
Benign
0.047
.;D;D
Sift4G
Uncertain
0.032
.;D;D
Polyphen
0.20
.;B;.
Vest4
0.10
MutPred
0.61
.;Loss of stability (P = 0.0726);.;
MVP
0.62
MPC
1.5
ClinPred
0.35
T
GERP RS
2.3
Varity_R
0.18
gMVP
0.24

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: rs1484434371; hg19: chr2-237123175; API