Genetic Variant ASB6:p.Asp419Tyr (chr9-129637801-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_017873.4(ASB6):c.1255G>T(p.Asp419Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000735 in 1,360,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

ASB6
NM_017873.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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=0.16199404).

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>T	p.Asp419Tyr	missense	Exon 6 of 6	NP_060343.1	Q9NWX5-1
ASB6	NM_001202403.2		c.1168G>T	p.Asp390Tyr	missense	Exon 5 of 5	NP_001189332.1	F6TX30
ASB6	NM_177999.3		c.*552G>T		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>T	p.Asp419Tyr	missense	Exon 6 of 6	ENSP00000277458.4	Q9NWX5-1
ASB6	ENST00000450050.6	TSL:1	c.1168G>T	p.Asp390Tyr	missense	Exon 5 of 5	ENSP00000416172.3	F6TX30
ASB6	ENST00000277459.8	TSL:1	c.*552G>T		3_prime_UTR	Exon 5 of 5	ENSP00000277459.4	Q9NWX5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000569

AC:

AN:

175690

AF XY:

0.0000108

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.35e-7

AC:

AN:

1360000

Hom.:

Cov.:

AF XY:

0.00000150

AC XY:

AN XY:

665196

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30134

American (AMR)

AF:

0.00

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:

0.0000143

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:

0.00

AC:

AN:

1062926

Other (OTH)

AF:

0.00

AC:

AN:

55880

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

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

Cov.:

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

0.13

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.028

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.13

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.68

M_CAP

Benign

0.081

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.75

MutationAssessor

Benign

1.2

PhyloP100

5.7

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.66

REVEL

Benign

0.14

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.0040

Polyphen

0.65

Vest4

0.27

MutPred

0.14

Gain of phosphorylation at D419 (P = 0.0434)

MVP

0.82

MPC

0.63

ClinPred

0.42

GERP RS

5.0

Varity_R

0.15

gMVP

0.49

Mutation Taster

=87/13

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over