rs3087684

Positions:

• chr3-57272291-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
APPL1	NM_012096.3	c.*2604T>C		3_prime_UTR_variant	22/22	ENST00000288266.8
ASB14	NM_001142733.3	c.*23-2673A>G		intron_variant		ENST00000487349.6
LOC105377102	NR_135535.1	n.186+2540T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APPL1	ENST00000288266.8	c.*2604T>C		3_prime_UTR_variant	22/22	1	NM_012096.3	P1
ASB14	ENST00000487349.6	c.*23-2673A>G		intron_variant		1	NM_001142733.3	P1
APPL1	ENST00000650354.1	c.*64+2540T>C		intron_variant, NMD_transcript_variant

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

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

Gnomad4 AFR AF: 0.728

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.924

Gnomad4 SAS AF: 0.647

Gnomad4 FIN AF: 0.693

Gnomad4 NFE AF: 0.606

Gnomad4 OTH AF: 0.654

Alfa AF: 0.622 Hom.: 30073

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

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

Other links and lift over

dbSNP: rs3087684; hg19: chr3-57306319;