Variant 1-75932260-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_080868.3(ASB17):c.32C>T(p.Thr11Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ASB17
NM_080868.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.43

Variant links:

Genes affected

ASB17 (HGNC:19769): (ankyrin repeat and SOCS box containing 17) Predicted to be involved in intracellular signal transduction and protein ubiquitination. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ASB17 links:

ASB17 (HGNC:):

ASB17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.093839884).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ASB17	NM_080868.3 linkuse as main transcript	c.32C>T	p.Thr11Ile	missense_variant	1/3	ENST00000284142.7	NP_543144.1
ASB17	XM_047445206.1 linkuse as main transcript	c.32C>T	p.Thr11Ile	missense_variant	1/3		XP_047301162.1
ASB17	NR_026546.3 linkuse as main transcript	n.145C>T		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASB17	ENST00000284142.7 linkuse as main transcript	c.32C>T	p.Thr11Ile	missense_variant	1/3	1	NM_080868.3	ENSP00000284142.6		Q8WXJ9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248514

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134572

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:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459536

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726014

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 01, 2024

The c.32C>T (p.T11I) alteration is located in exon 1 (coding exon 1) of the ASB17 gene. This alteration results from a C to T substitution at nucleotide position 32, causing the threonine (T) at amino acid position 11 to be replaced by an isoleucine (I). 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

0.12

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.014

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.59

M_CAP

Benign

0.0056

MetaRNN

Benign

0.094

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.46

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.6

REVEL

Benign

0.031

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0060

Polyphen

0.0020

Vest4

0.16

MutPred

0.29

Loss of relative solvent accessibility (P = 0.0186);

MVP

0.39

MPC

0.15

ClinPred

0.47

GERP RS

4.2

Varity_R

0.10

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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