NM_001142733.3:c.*1149T>C
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_001142733.3(ASB14):c.*1149T>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 0.00000414 in 1,448,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
ASB14
NM_001142733.3 3_prime_UTR
NM_001142733.3 3_prime_UTR
Scores
2
Splicing: ADA: 0.00004452
2
Clinical Significance
Conservation
PhyloP100: 0.805
Genes affected
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]
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 3-57268492-A-G is Benign according to our data. Variant chr3-57268492-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3034768.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ASB14 | NM_001142733.3 | c.*1149T>C | 3_prime_UTR_variant | Exon 11 of 11 | ENST00000487349.6 | NP_001136205.2 | ||
APPL1 | NM_012096.3 | c.1983+5A>G | splice_region_variant, intron_variant | Intron 21 of 21 | ENST00000288266.8 | NP_036228.1 | ||
ASB14 | NM_130387.5 | c.*1149T>C | 3_prime_UTR_variant | Exon 4 of 4 | NP_569058.1 | |||
APPL1 | XM_011533583.4 | c.1932+5A>G | splice_region_variant, intron_variant | Intron 22 of 22 | XP_011531885.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ASB14 | ENST00000487349 | c.*1149T>C | 3_prime_UTR_variant | Exon 11 of 11 | 1 | NM_001142733.3 | ENSP00000419199.1 | |||
APPL1 | ENST00000288266.8 | c.1983+5A>G | splice_region_variant, intron_variant | Intron 21 of 21 | 1 | NM_012096.3 | ENSP00000288266.3 | |||
ASB14 | ENST00000389601 | c.*1149T>C | 3_prime_UTR_variant | Exon 12 of 12 | ||||||
APPL1 | ENST00000650354.1 | n.1983+5A>G | splice_region_variant, intron_variant | Intron 21 of 23 | ENSP00000498115.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000167 AC: 4AN: 240232Hom.: 0 AF XY: 0.00000768 AC XY: 1AN XY: 130284
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GnomAD4 exome AF: 0.00000414 AC: 6AN: 1448876Hom.: 0 Cov.: 30 AF XY: 0.00000277 AC XY: 2AN XY: 721000
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GnomAD4 genome Cov.: 32
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32
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
APPL1-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 25, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at