Genetic Variant ASB18:p.Gly326Arg (chr2-236214487-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_212556.4(ASB18):c.976G>A(p.Gly326Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G326W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ASB18
NM_212556.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.44

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.833

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_212556.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASB18	NM_212556.4	MANE Select	c.976G>A	p.Gly326Arg	missense	Exon 4 of 6	NP_997721.2	Q6ZVZ8-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASB18	ENST00000409749.8	TSL:1 MANE Select	c.976G>A	p.Gly326Arg	missense	Exon 4 of 6	ENSP00000386532.3	Q6ZVZ8-1
ASB18	ENST00000645891.1		c.889G>A	p.Gly297Arg	missense	Exon 3 of 5	ENSP00000496134.1	Q6ZVZ8-2
ASB18	ENST00000447030.1	TSL:4	c.115G>A	p.Gly39Arg	missense	Exon 1 of 2	ENSP00000411434.1	H7C3E8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1356554

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

669606

African (AFR)

AF:

0.00

AC:

AN:

27296

American (AMR)

AF:

0.00

AC:

AN:

32284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23960

East Asian (EAS)

AF:

0.00

AC:

AN:

32270

South Asian (SAS)

AF:

0.00

AC:

AN:

77504

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33542

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4320

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1068840

Other (OTH)

AF:

0.00

AC:

AN:

56538

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.84

M_CAP

Pathogenic

0.45

MetaRNN

Pathogenic

0.83

MetaSVM

Uncertain

-0.18

MutationAssessor

Pathogenic

3.2

PhyloP100

6.4

PrimateAI

Pathogenic

0.91

PROVEAN

Pathogenic

-7.0

REVEL

Uncertain

0.42

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.039

Polyphen

1.0

Vest4

0.69

MutPred

0.63

Gain of methylation at G326 (P = 0.0613)

MVP

0.64

MPC

2.4

ClinPred

0.99

GERP RS

3.0

PromoterAI

-0.028

Neutral

(source)

Varity_R

0.51

gMVP

0.53

Mutation Taster

=69/31

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over