Genetic Variant ASB6:p.Asp419Asn (chr9-129637801-C-T) – 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_017873.4(ASB6):c.1255G>A(p.Asp419Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000443 in 1,512,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. D419Y) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

ASB6
NM_017873.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.66

Publications

0 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:

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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=0.10602632).

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.1255G>A	p.Asp419Asn	missense	Exon 6 of 6	NP_060343.1	Q9NWX5-1
ASB6	NM_001202403.2		c.1168G>A	p.Asp390Asn	missense	Exon 5 of 5	NP_001189332.1	F6TX30
ASB6	NM_177999.3		c.*552G>A		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.1255G>A	p.Asp419Asn	missense	Exon 6 of 6	ENSP00000277458.4	Q9NWX5-1
ASB6	ENST00000450050.6	TSL:1	c.1168G>A	p.Asp390Asn	missense	Exon 5 of 5	ENSP00000416172.3	F6TX30
ASB6	ENST00000277459.8	TSL:1	c.*552G>A		3_prime_UTR	Exon 5 of 5	ENSP00000277459.4	Q9NWX5-2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000228

AC:

AN:

175690

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000654

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000233

Gnomad OTH exome

AF:

0.000250

GnomAD4 exome

AF:

0.0000463

AC:

AN:

1360000

Hom.:

Cov.:

AF XY:

0.0000496

AC XY:

AN XY:

665196

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30134

American (AMR)

AF:

0.0000352

AC:

AN:

28424

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19798

East Asian (EAS)

AF:

0.00

AC:

AN:

38588

South Asian (SAS)

AF:

0.00

AC:

AN:

69714

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49262

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5274

European-Non Finnish (NFE)

AF:

0.0000546

AC:

AN:

1062926

Other (OTH)

AF:

0.0000716

AC:

AN:

55880

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

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:

0.0000263

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41466

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68052

Other (OTH)

AF:

0.000478

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000638

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000171

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.025

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.30

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.71

M_CAP

Benign

0.043

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.2

PhyloP100

5.7

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.25

REVEL

Benign

0.10

Sift

Benign

0.13

Sift4G

Uncertain

0.018

Polyphen

0.0

Vest4

0.16

MutPred

0.12

Loss of stability (P = 0.091)

MVP

0.67

MPC

0.34

ClinPred

0.41

GERP RS

5.0

Varity_R

0.078

gMVP

0.30

Mutation Taster

=89/11

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