Variant 9-129637813-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017873.4(ASB6):c.1243G>A(p.Gly415Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000734 in 1,362,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: 7.3e-7 ( 0 hom. )

Consequence

ASB6
NM_017873.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0680

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04995209).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASB6	NM_017873.4 link	c.1243G>A	p.Gly415Ser	missense_variant	6/6	ENST00000277458.5	NP_060343.1	Q9NWX5-1
ASB6	NM_001202403.2 link	c.1156G>A	p.Gly386Ser	missense_variant	5/5		NP_001189332.1	Q9NWX5F6TX30
ASB6	NM_177999.3 link	c.*540G>A		3_prime_UTR_variant	5/5		NP_821066.1	Q9NWX5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ASB6	ENST00000277458.5 link	c.1243G>A	p.Gly415Ser	missense_variant	6/6	1	NM_017873.4	ENSP00000277458.4	Q9NWX5-1
ASB6	ENST00000450050.6 link	c.1156G>A	p.Gly386Ser	missense_variant	5/5	1		ENSP00000416172.3	F6TX30
ASB6	ENST00000277459 link	c.*540G>A		3_prime_UTR_variant	5/5	1		ENSP00000277459.4	Q9NWX5-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000565

AC:

AN:

176926

Hom.:

AF XY:

0.0000108

AC XY:

AN XY:

92988

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000116

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.34e-7

AC:

AN:

1362248

Hom.:

Cov.:

AF XY:

0.00000150

AC XY:

AN XY:

666526

show subpopulations

Gnomad4 AFR exome

AF:

0.0000332

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 01, 2022

The c.1243G>A (p.G415S) alteration is located in exon 6 (coding exon 6) of the ASB6 gene. This alteration results from a G to A substitution at nucleotide position 1243, causing the glycine (G) at amino acid position 415 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

2.0

DANN

Benign

0.82

DEOGEN2

Benign

0.13

T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.041

MetaRNN

Benign

0.050

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

.;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.28

.;N

REVEL

Benign

0.059

Sift

Benign

0.31

.;T

Sift4G

Benign

0.38

T;T

Polyphen

0.0

.;B

Vest4

0.11

MutPred

0.22

.;Loss of glycosylation at S414 (P = 0.0384);

MVP

0.49

MPC

0.34

ClinPred

0.047

GERP RS

-0.69

Varity_R

0.057

gMVP

0.36

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over