Variant chr3-57227866-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_012096.3(APPL1):c.-18C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0133 in 1,458,332 control chromosomes in the GnomAD database, including 2,171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.071 ( 1268 hom., cov: 33)

Exomes 𝑓: 0.0066 ( 903 hom. )

Consequence

APPL1
NM_012096.3 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.226

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 3-57227866-C-T is Benign according to our data. Variant chr3-57227866-C-T is described in ClinVar as [Benign]. Clinvar id is 1251769.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.239 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.-18C>T		5_prime_UTR_variant	1/22	ENST00000288266.8
APPL1	XM_011533583.4 linkuse as main transcript	c.-123C>T		5_prime_UTR_variant	1/23

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APPL1	ENST00000288266.8 linkuse as main transcript	c.-18C>T		5_prime_UTR_variant	1/22	1	NM_012096.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0705

AC:

10710

AN:

151902

Hom.:

1265

Cov.:

show subpopulations

Gnomad AFR

AF:

0.243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0289

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0318

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.0550

GnomAD3 exomes

AF:

0.00930

AC:

854

AN:

91852

Hom.:

AF XY:

0.00650

AC XY:

335

AN XY:

51506

show subpopulations

Gnomad AFR exome

AF:

0.261

Gnomad AMR exome

AF:

0.0129

Gnomad ASJ exome

AF:

0.00658

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000603

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000705

Gnomad OTH exome

AF:

0.00659

GnomAD4 exome

AF:

0.00661

AC:

8635

AN:

1306322

Hom.:

903

Cov.:

AF XY:

0.00580

AC XY:

3740

AN XY:

644428

show subpopulations

Gnomad4 AFR exome

AF:

0.249

Gnomad4 AMR exome

AF:

0.0157

Gnomad4 ASJ exome

AF:

0.00542

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000569

Gnomad4 FIN exome

AF:

0.0000286

Gnomad4 NFE exome

AF:

0.000420

Gnomad4 OTH exome

AF:

0.0169

GnomAD4 genome

AF:

0.0707

AC:

10746

AN:

152010

Hom.:

1268

Cov.:

AF XY:

0.0698

AC XY:

5191

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.243

Gnomad4 AMR

AF:

0.0289

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.0545

Alfa

AF:

0.0496

Hom.:

122

Bravo

AF:

0.0795

Asia WGS

AF:

0.0120

AC:

AN:

3412

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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