Variant 3-57238122-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012096.3(APPL1):c.285+6C>T variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00892 in 1,598,026 control chromosomes in the GnomAD database, including 1,061 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 587 hom., cov: 33)

Exomes 𝑓: 0.0049 ( 474 hom. )

Consequence

APPL1
NM_012096.3 splice_donor_region, intron

Scores

Splicing: ADA: 0.00001799

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.743

Variant links:

Genes affected

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 3-57238122-C-T is Benign according to our data. Variant chr3-57238122-C-T is described in ClinVar as [Benign]. Clinvar id is 1169476.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APPL1	NM_012096.3 linkuse as main transcript	c.285+6C>T		splice_donor_region_variant, intron_variant		ENST00000288266.8
APPL1	XM_011533583.4 linkuse as main transcript	c.234+6C>T		splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APPL1	ENST00000288266.8 linkuse as main transcript	c.285+6C>T		splice_donor_region_variant, intron_variant		1	NM_012096.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0470

AC:

7153

AN:

152034

Hom.:

586

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0233

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.000794

Gnomad OTH

AF:

0.0398

GnomAD3 exomes

AF:

0.0126

AC:

3059

AN:

243104

Hom.:

199

AF XY:

0.00909

AC XY:

1193

AN XY:

131224

show subpopulations

Gnomad AFR exome

AF:

0.158

Gnomad AMR exome

AF:

0.0109

Gnomad ASJ exome

AF:

0.00633

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000142

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000692

Gnomad OTH exome

AF:

0.00605

GnomAD4 exome

AF:

0.00490

AC:

7081

AN:

1445874

Hom.:

474

Cov.:

AF XY:

0.00426

AC XY:

3064

AN XY:

719066

show subpopulations

Gnomad4 AFR exome

AF:

0.160

Gnomad4 AMR exome

AF:

0.0119

Gnomad4 ASJ exome

AF:

0.00533

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000204

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000376

Gnomad4 OTH exome

AF:

0.0117

GnomAD4 genome

AF:

0.0472

AC:

7176

AN:

152152

Hom.:

587

Cov.:

AF XY:

0.0470

AC XY:

3496

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.160

Gnomad4 AMR

AF:

0.0232

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000794

Gnomad4 OTH

AF:

0.0393

Alfa

AF:

0.0235

Hom.:

109

Bravo

AF:

0.0533

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 05, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000018

dbscSNV1_RF

Benign

0.0020

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