Genetic Variant NM_080863.5:c.430C>T (chr17-44172174-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_080863.5(ASB16):c.430C>T(p.Arg144Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000936 in 1,612,514 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R144H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00056 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000045 ( 0 hom. )

Consequence

ASB16
NM_080863.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.345

Publications

0 publications found

Variant links:

Genes affected

ASB16 (HGNC:19768): (ankyrin repeat and SOCS box containing 16) 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, Jul 2008]

ASB16 links:

ASB16-AS1 (HGNC:25442): (ASB16 antisense RNA 1)

ASB16-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009508848).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080863.5. 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
	ASB16	NM_080863.5	MANE Select	c.430C>T	p.Arg144Cys	missense	Exon 2 of 5	NP_543139.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASB16	ENST00000293414.6	TSL:1 MANE Select	c.430C>T	p.Arg144Cys	missense	Exon 2 of 5	ENSP00000293414.1	Q96NS5
ASB16	ENST00000589618.1	TSL:1	n.430C>T		non_coding_transcript_exon	Exon 2 of 5	ENSP00000466033.1	K7ELE0
ASB16	ENST00000591700.1	TSL:4	c.178C>T	p.Arg60Cys	missense	Exon 3 of 3	ENSP00000466349.1	K7EM41

Frequencies

GnomAD3 genomes

AF:

0.000552

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00188

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000172

AC:

AN:

250032

AF XY:

0.000103

show subpopulations

Gnomad AFR exome

AF:

0.00234

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000452

AC:

AN:

1460244

Hom.:

Cov.:

AF XY:

0.0000454

AC XY:

AN XY:

726528

show subpopulations

African (AFR)

AF:

0.00125

AC:

AN:

33478

American (AMR)

AF:

0.000112

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51802

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000989

AC:

AN:

1112000

Other (OTH)

AF:

0.0000828

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000558

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.00190

AC:

AN:

41564

American (AMR)

AF:

0.000196

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68020

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000250

Hom.:

Bravo

AF:

0.000650

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000239

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.17

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.025

MetaRNN

Benign

0.0095

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.99

PhyloP100

-0.34

PrimateAI

Benign

0.40

PROVEAN

Pathogenic

-4.7

REVEL

Benign

0.20

Sift

Uncertain

0.0080

Sift4G

Pathogenic

0.0010

Polyphen

0.27

Vest4

0.50

MVP

0.39

MPC

0.46

ClinPred

0.10

GERP RS

4.5

Varity_R

0.23

gMVP

0.53

Mutation Taster

=78/22

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over