3-57272583-C-A

Position:

• chr3-57272583-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012096.3(APPL1):​c.*2896C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 151,862 control chromosomes in the GnomAD database, including 2,840 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 0.18 (2840 hom., cov: 31)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: APPL1 NM_012096.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.148

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APPL1	NM_012096.3	c.*2896C>A		3_prime_UTR_variant	22/22	ENST00000288266.8
ASB14	NM_001142733.3	c.*23-2965G>T		intron_variant		ENST00000487349.6
LOC105377102	NR_135535.1	n.186+2832C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APPL1	ENST00000288266.8	c.*2896C>A		3_prime_UTR_variant	22/22	1	NM_012096.3	P1
ASB14	ENST00000487349.6	c.*23-2965G>T		intron_variant		1	NM_001142733.3	P1
APPL1	ENST00000650354.1	c.*64+2832C>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27707 AN: 151702 Hom.: 2832 Cov.: 31

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.0441

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.173

GnomAD4 exome AF: 0.167 AC: 7 AN: 42 Hom.: 0 Cov.: 0 AF XY: 0.147 AC XY: 5 AN XY: 34

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome AF: 0.183 AC: 27745 AN: 151820 Hom.: 2840 Cov.: 31 AF XY: 0.178 AC XY: 13228 AN XY: 74180

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.0441

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.171

Alfa AF: 0.173 Hom.: 2310

Bravo AF: 0.185

Asia WGS AF: 0.0670 AC: 234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.3
DANN	Benign	0.71

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: rs17791685; hg19: chr3-57306611;