Variant 3-57227919-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_012096.3(APPL1):c.36G>C(p.Thr12=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00529 in 1,464,962 control chromosomes in the GnomAD database, including 183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0088 ( 38 hom., cov: 33)

Exomes 𝑓: 0.0049 ( 145 hom. )

Consequence

APPL1
NM_012096.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.265

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 3-57227919-G-C is Benign according to our data. Variant chr3-57227919-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1183160.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.265 with no splicing effect.

BS2

High AC in GnomAd4 at 1337 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APPL1	NM_012096.3 linkuse as main transcript	c.36G>C	p.Thr12=	synonymous_variant	1/22	ENST00000288266.8
APPL1	XM_011533583.4 linkuse as main transcript	c.-70G>C		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.36G>C	p.Thr12=	synonymous_variant	1/22	1	NM_012096.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00880

AC:

1337

AN:

151984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000266

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.0657

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00890

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00827

AC:

794

AN:

96026

Hom.:

AF XY:

0.00789

AC XY:

421

AN XY:

53332

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000211

Gnomad ASJ exome

AF:

0.00304

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00147

Gnomad FIN exome

AF:

0.0615

Gnomad NFE exome

AF:

0.00557

Gnomad OTH exome

AF:

0.00653

GnomAD4 exome

AF:

0.00489

AC:

6415

AN:

1312870

Hom.:

145

Cov.:

AF XY:

0.00508

AC XY:

3287

AN XY:

647444

show subpopulations

Gnomad4 AFR exome

AF:

0.0000373

Gnomad4 AMR exome

AF:

0.000169

Gnomad4 ASJ exome

AF:

0.00317

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00132

Gnomad4 FIN exome

AF:

0.0661

Gnomad4 NFE exome

AF:

0.00330

Gnomad4 OTH exome

AF:

0.00432

GnomAD4 genome

AF:

0.00879

AC:

1337

AN:

152092

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

797

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0657

Gnomad4 NFE

AF:

0.00890

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.0108

Hom.:

Bravo

AF:

0.00270

Asia WGS

AF:

0.00147

AC:

AN:

3424

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 26, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 10, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	APPL1: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jun 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

9.9

DANN

Benign

0.83

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