7-151176613-C-T

Position:

chr7-151176613-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBS2_Supporting

The NM_001142459.2(ASB10):c.1168G>A(p.Val390Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,551,338 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

ASB10
NM_001142459.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.11

Variant links:

Genes affected

ASB10 (HGNC:17185): (ankyrin repeat and SOCS box containing 10) The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. The SOCS box serves to couple suppressor of cytokine signaling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. Multiple alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Dec 2008]

ASB10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.117951125).

BP6

Variant 7-151176613-C-T is Benign according to our data. Variant chr7-151176613-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2354499.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 9 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASB10	NM_001142459.2 linkuse as main transcript	c.1168G>A	p.Val390Met	missense_variant	4/6	ENST00000420175.3	NP_001135931.2	Q8WXI3-1
ASB10	NM_080871.4 linkuse as main transcript	c.1123G>A	p.Val375Met	missense_variant	4/6		NP_543147.2	Q8WXI3-3
ASB10	NM_001142460.1 linkuse as main transcript	c.1105-316G>A		intron_variant			NP_001135932.2	Q8WXI3-2A0A090N8I2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ASB10	ENST00000420175.3 linkuse as main transcript	c.1168G>A	p.Val390Met	missense_variant	4/6	1	NM_001142459.2	ENSP00000391137.2	Q8WXI3-1
ASB10	ENST00000275838.5 linkuse as main transcript	c.1105-316G>A		intron_variant		1		ENSP00000275838.1	Q8WXI3-2
ASB10	ENST00000377867.7 linkuse as main transcript	c.1123G>A	p.Val375Met	missense_variant	4/6	2		ENSP00000367098.3	Q8WXI3-3

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000637

AC:

AN:

156870

Hom.:

AF XY:

0.00

AC XY:

AN XY:

83098

show subpopulations

Gnomad AFR exome

AF:

0.000126

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000643

AC:

AN:

1399178

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

690064

show subpopulations

Gnomad4 AFR exome

AF:

0.000253

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:

0.0000172

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000680

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.53

CADD

Benign

7.8

DANN

Benign

0.87

DEOGEN2

Benign

0.035

.;T

Eigen

Benign

-0.98

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.74

.;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.083

Sift

Benign

0.14

T;T

Sift4G

Benign

0.11

T;T

Polyphen

0.054

B;B

Vest4

0.085

MutPred

0.51

.;Loss of catalytic residue at V390 (P = 0.0854);

MVP

0.46

MPC

0.059

ClinPred

0.044

GERP RS

0.18

Varity_R

0.046

gMVP

0.18

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