chr3-57276572-C-T

Position:

chr3-57276572-C-T

Variant summary

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

The NM_001142733.3(ASB14):c.1742G>A(p.Gly581Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000883 in 1,608,490 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: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000094 ( 0 hom. )

Consequence

ASB14
NM_001142733.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.840

Variant links:

Genes affected

ASB14 (HGNC:19766): (ankyrin repeat and SOCS box containing 14) The protein encoded by this gene is a member of the ankyrin repeat and SOCS box-containing (ASB) family of proteins. They contain ankyrin repeat sequence and a SOCS box domain. The SOCS box serves to couple suppressor of cytokine signalling (SOCS) proteins and their binding partners with the elongin B and C complex, possibly targeting them for degradation. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Dec 2008]

ASB14 links:

LOC105377102 (HGNC:):

LOC105377102 links:

APPL1 (HGNC:24035): (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1) The protein encoded by this gene has been shown to be involved in the regulation of cell proliferation, and in the crosstalk between the adiponectin signalling and insulin signalling pathways. The encoded protein binds many other proteins, including RAB5A, DCC, AKT2, PIK3CA, adiponectin receptors, and proteins of the NuRD/MeCP1 complex. This protein is found associated with endosomal membranes, but can be released by EGF and translocated to the nucleus. [provided by RefSeq, Jul 2008]

APPL1 links:

Genome browser will be placed here

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=0.042289197).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASB14	NM_001142733.3 linkuse as main transcript	c.1742G>A	p.Gly581Glu	missense_variant	10/11	ENST00000487349.6	NP_001136205.2
LOC105377102	NR_135535.1 linkuse as main transcript	n.342+113C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASB14	ENST00000487349.6 linkuse as main transcript	c.1742G>A	p.Gly581Glu	missense_variant	10/11	1	NM_001142733.3	ENSP00000419199	P1	A6NK59-3
ASB14	ENST00000515033.1 linkuse as main transcript	n.887G>A		non_coding_transcript_exon_variant	3/3	1
APPL1	ENST00000650354.1 linkuse as main transcript	c.*220+113C>T		intron_variant, NMD_transcript_variant				ENSP00000498115

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.00

GnomAD3 exomes

AF:

0.0000364

AC:

AN:

246978

Hom.:

AF XY:

0.0000601

AC XY:

AN XY:

133190

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:

0.0000799

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000941

AC:

137

AN:

1456416

Hom.:

Cov.:

AF XY:

0.0000856

AC XY:

AN XY:

724082

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:

0.000112

Gnomad4 OTH exome

AF:

0.000216

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152074

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000110

EpiControl

AF:

0.000119

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

Mar 01, 2023

The c.1742G>A (p.G581E) alteration is located in exon 10 (coding exon 9) of the ASB14 gene. This alteration results from a G to A substitution at nucleotide position 1742, causing the glycine (G) at amino acid position 581 to be replaced by a glutamic acid (E). 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

0.074

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.041

.;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.042

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.46

N;N

MutationTaster

Benign

0.62

D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.42

N;N

REVEL

Benign

0.034

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Vest4

0.16

MutPred

0.36

Gain of glycosylation at Y578 (P = 0.0299);Gain of glycosylation at Y578 (P = 0.0299);

MVP

0.30

MPC

0.031

ClinPred

0.066

GERP RS

3.6

Varity_R

0.038

gMVP

0.70

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