Variant 2-236214363-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_212556.4(ASB18):c.1100A>G(p.Lys367Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000281 in 1,421,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

ASB18
NM_212556.4 missense, splice_region

Scores

Splicing: ADA: 0.9896

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.82

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]

ASB18 links:

GBX2-AS1 (HGNC:55714): (GBX2 and ASB18 antisense RNA 1)

GBX2-AS1 links:

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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/exons	MANE	Protein	UniProt
ASB18	NM_212556.4 linkuse as main transcript	c.1100A>G	p.Lys367Arg	missense_variant, splice_region_variant	4/6	ENST00000409749.8	NP_997721.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASB18	ENST00000409749.8 linkuse as main transcript	c.1100A>G	p.Lys367Arg	missense_variant, splice_region_variant	4/6	1	NM_212556.4	ENSP00000386532	P1	Q6ZVZ8-1
GBX2-AS1	ENST00000415226.1 linkuse as main transcript	n.224-45144T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000281

AC:

AN:

1421714

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

704450

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:

0.00000365

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000378

Hom.:

ExAC

AF:

0.00000844

AC:

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 submitter

clinical testing

Ambry Genetics

Aug 22, 2023

The c.1100A>G (p.K367R) alteration is located in exon 4 (coding exon 4) of the ASB18 gene. This alteration results from a A to G substitution at nucleotide position 1100, causing the lysine (K) at amino acid position 367 to be replaced by an arginine (R). 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

0.13

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.045

.;T;.

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.73

T;T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.30

T;T;T

MetaSVM

Benign

-0.75

MutationAssessor

Pathogenic

3.2

.;M;.

MutationTaster

Benign

0.95

D;D

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-2.3

.;N;D

REVEL

Benign

0.14

Sift

Benign

0.059

.;T;D

Sift4G

Benign

0.071

.;T;T

Polyphen

1.0

.;D;.

Vest4

0.15

MVP

0.25

MPC

1.1

ClinPred

0.66

GERP RS

3.9

Varity_R

0.18

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.90

SpliceAI score (max)

0.12

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over