Genetic Variant ASB6:p.Val396Leu (chr9-129637870-C-G) – 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_017873.4(ASB6):c.1186G>C(p.Val396Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000433 in 1,549,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

ASB6
NM_017873.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.63

Publications

1 publications found

Variant links:

Genes affected

ASB6 (HGNC:17181): (ankyrin repeat and SOCS box containing 6) The protein encoded by this gene belongs to a family of ankyrin repeat proteins that, along with four other protein families, contain a C-terminal SOCS box motif. Growing evidence suggests that the SOCS box, similar to the F-box, acts as a bridge between specific substrate-binding domains and the more generic proteins that comprise a large family of E3 ubiquitin protein ligases. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Jan 2011]

ASB6 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=0.029860377).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017873.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASB6	NM_017873.4	MANE Select	c.1186G>C	p.Val396Leu	missense	Exon 6 of 6	NP_060343.1	Q9NWX5-1
ASB6	NM_001202403.2		c.1099G>C	p.Val367Leu	missense	Exon 5 of 5	NP_001189332.1	F6TX30
ASB6	NM_177999.3		c.*483G>C		3_prime_UTR	Exon 5 of 5	NP_821066.1	Q9NWX5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ASB6	ENST00000277458.5	TSL:1 MANE Select	c.1186G>C	p.Val396Leu	missense	Exon 6 of 6	ENSP00000277458.4	Q9NWX5-1
ASB6	ENST00000450050.6	TSL:1	c.1099G>C	p.Val367Leu	missense	Exon 5 of 5	ENSP00000416172.3	F6TX30
ASB6	ENST00000277459.8	TSL:1	c.*483G>C		3_prime_UTR	Exon 5 of 5	ENSP00000277459.4	Q9NWX5-2

Frequencies

GnomAD3 genomes

AF:

0.0000525

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.000478

GnomAD2 exomes

AF:

0.0000952

AC:

AN:

199662

AF XY:

0.0000849

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000495

Gnomad ASJ exome

AF:

0.000926

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000108

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000422

AC:

AN:

1396740

Hom.:

Cov.:

AF XY:

0.0000509

AC XY:

AN XY:

687810

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31390

American (AMR)

AF:

0.000540

AC:

AN:

35208

Ashkenazi Jewish (ASJ)

AF:

0.000966

AC:

AN:

21732

East Asian (EAS)

AF:

0.00

AC:

AN:

39162

South Asian (SAS)

AF:

0.00

AC:

AN:

75046

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50982

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5428

European-Non Finnish (NFE)

AF:

0.00000833

AC:

AN:

1080290

Other (OTH)

AF:

0.000174

AC:

AN:

57502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

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:

0.0000525

AC:

AN:

152356

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41592

American (AMR)

AF:

0.000392

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68040

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.00

Hom.:

Bravo

AF:

0.0000945

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000413

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

Pathogenic

0.57

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.032

Eigen

Benign

-0.076

Eigen_PC

Benign

0.033

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.013

MetaRNN

Benign

0.030

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

1.6

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.69

REVEL

Benign

0.14

Sift

Benign

0.20

Sift4G

Uncertain

0.019

Polyphen

0.027

Vest4

0.12

MVP

0.28

MPC

0.47

ClinPred

0.088

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.090

gMVP

0.60

Mutation Taster

=81/19

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over