3-57228000-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012096.3(APPL1):c.54+63C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00943 in 1,321,942 control chromosomes in the GnomAD database, including 967 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.047 (591 hom., cov: 33)
  • Exomes 𝑓: 0.0045 (376 hom.)
• Consequence: APPL1 NM_012096.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.08

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 3-57228000-C-T is Benign according to our data. Variant chr3-57228000-C-T is described in ClinVar as [Benign]. Clinvar id is 1261640.Status of the report is criteria_provided_single_submitter, 1 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	c.54+63C>T		intron_variant		ENST00000288266.8
APPL1	XM_011533583.4	c.-52+63C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APPL1	ENST00000288266.8	c.54+63C>T		intron_variant		1	NM_012096.3	P1

Frequencies

GnomAD3 genomes AF: 0.0471 AC: 7151 AN: 151856 Hom.: 590 Cov.: 33

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0233

Gnomad ASJ AF: 0.00462

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.000780

Gnomad OTH AF: 0.0388

GnomAD4 exome AF: 0.00453 AC: 5298 AN: 1169978 Hom.: 376 AF XY: 0.00400 AC XY: 2280 AN XY: 569786

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.0131

Gnomad4 ASJ exome AF: 0.00547

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000249

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000354

Gnomad4 OTH exome AF: 0.0122

GnomAD4 genome AF: 0.0472 AC: 7174 AN: 151964 Hom.: 591 Cov.: 33 AF XY: 0.0470 AC XY: 3494 AN XY: 74306

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.0233

Gnomad4 ASJ AF: 0.00462

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000827

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000780

Gnomad4 OTH AF: 0.0384

Alfa AF: 0.0350 Hom.: 36

Bravo AF: 0.0533

Asia WGS AF: 0.00732 AC: 26 AN: 3430

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	5.8
Dann	Benign	0.89

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs7643764; hg19: chr3-57262028;