rs3087684

Variant names:

• chr3-57272291-T-C
• rs3087684
• NM_012096.3:c.*2604T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012096.3(APPL1):​c.*2604T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 151,998 control chromosomes in the GnomAD database, including 34,567 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.67 (34567 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: APPL1 NM_012096.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.209
• Publications: 12 publications found

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]

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]

LOC105377102 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APPL1	NM_012096.3	c.*2604T>C		3_prime_UTR_variant	Exon 22 of 22	ENST00000288266.8	NP_036228.1
ASB14	NM_001142733.3	c.*23-2673A>G		intron_variant	Intron 10 of 10	ENST00000487349.6	NP_001136205.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APPL1	ENST00000288266.8	c.*2604T>C		3_prime_UTR_variant	Exon 22 of 22	1	NM_012096.3	ENSP00000288266.3
ASB14	ENST00000487349.6	c.*23-2673A>G		intron_variant	Intron 10 of 10	1	NM_001142733.3	ENSP00000419199.1
APPL1	ENST00000650354.1	n.*64+2540T>C		intron_variant	Intron 22 of 23			ENSP00000498115.1

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101759 AN: 151880 Hom.: 34510 Cov.: 31

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.924

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.650

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.670 AC: 101874 AN: 151998 Hom.: 34567 Cov.: 31 AF XY: 0.675 AC XY: 50159 AN XY: 74292

African (AFR) AF: 0.728 AC: 30183 AN: 41464

American (AMR) AF: 0.740 AC: 11313 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 1932 AN: 3468

East Asian (EAS) AF: 0.924 AC: 4772 AN: 5164

South Asian (SAS) AF: 0.647 AC: 3110 AN: 4810

European-Finnish (FIN) AF: 0.693 AC: 7311 AN: 10548

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.606 AC: 41171 AN: 67948

Other (OTH) AF: 0.654 AC: 1382 AN: 2112

Alfa AF: 0.628 Hom.: 39773

Bravo AF: 0.677

Asia WGS AF: 0.781 AC: 2712 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.0
DANN	Benign	0.70
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3087684; hg19: chr3-57306319;