Genetic Variant NM_024701.4:c.11G>T (chr10-5666541-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024701.4(ASB13):c.11G>T(p.Arg4Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000918 in 1,089,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign 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. R4Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 9.2e-7 ( 0 hom. )

Consequence

ASB13
NM_024701.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.167

Publications

0 publications found

Variant links:

Genes affected

ASB13 (HGNC:19765): (ankyrin repeat and SOCS box containing 13) 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. Multiple alternatively spliced transcript variants, both protein-coding and not protein-coding, have been described for this gene. [provided by RefSeq, Nov 2010]

ASB13 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18877503).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024701.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ASB13	NM_024701.4	MANE Select	c.11G>T	p.Arg4Leu	missense	Exon 1 of 6	NP_078977.2
ASB13	NR_024581.2		n.55G>T		non_coding_transcript_exon	Exon 1 of 5
ASB13	NR_037164.2		n.55G>T		non_coding_transcript_exon	Exon 1 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASB13	ENST00000357700.11	TSL:1 MANE Select	c.11G>T	p.Arg4Leu	missense	Exon 1 of 6	ENSP00000350331.6	Q8WXK3-1
ASB13	ENST00000459912.5	TSL:1	n.11G>T		non_coding_transcript_exon	Exon 1 of 7	ENSP00000433358.1	Q8WXK3-2
ASB13	ENST00000904595.1		c.11G>T	p.Arg4Leu	missense	Exon 1 of 5	ENSP00000574654.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.18e-7

AC:

AN:

1089462

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

524242

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

22074

American (AMR)

AF:

0.00

AC:

AN:

12158

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14400

East Asian (EAS)

AF:

0.00

AC:

AN:

23082

South Asian (SAS)

AF:

0.0000316

AC:

AN:

31620

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21328

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2870

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

919798

Other (OTH)

AF:

0.00

AC:

AN:

42132

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.030

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.56

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

0.17

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.41

REVEL

Benign

0.10

Sift

Benign

0.067

Sift4G

Uncertain

0.037

Polyphen

0.25

Vest4

0.41

MutPred

0.49

Loss of solvent accessibility (P = 0.0299)

MVP

0.47

MPC

0.18

ClinPred

0.25

GERP RS

2.1

PromoterAI

0.050

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.094

gMVP

0.34

Mutation Taster

=95/5

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

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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