rs753541585
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_016824.5(ADD3):c.*2_*5del variant causes a stop retained, 3 prime UTR change. The variant allele was found at a frequency of 0.000251 in 1,570,816 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00025 ( 0 hom. )
Consequence
ADD3
NM_016824.5 stop_retained, 3_prime_UTR
NM_016824.5 stop_retained, 3_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.44
Genes affected
ADD3 (HGNC:245): (adducin 3) Adducins are heteromeric proteins composed of different subunits referred to as adducin alpha, beta and gamma. The three subunits are encoded by distinct genes and belong to a family of membrane skeletal proteins involved in the assembly of spectrin-actin network in erythrocytes and at sites of cell-cell contact in epithelial tissues. While adducins alpha and gamma are ubiquitously expressed, the expression of adducin beta is restricted to brain and hematopoietic tissues. Adducin, originally purified from human erythrocytes, was found to be a heterodimer of adducins alpha and beta. Polymorphisms resulting in amino acid substitutions in these two subunits have been associated with the regulation of blood pressure in an animal model of hypertension. Heterodimers consisting of alpha and gamma subunits have also been described. Structurally, each subunit is comprised of two distinct domains. The amino-terminal region is protease resistant and globular in shape, while the carboxy-terminal region is protease sensitive. The latter contains multiple phosphorylation sites for protein kinase C, the binding site for calmodulin, and is required for association with spectrin and actin. Alternatively spliced adducin gamma transcripts encoding different isoforms have been described. The functions of the different isoforms are not known. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP6
?
Variant 10-110133615-CTAAA-C is Benign according to our data. Variant chr10-110133615-CTAAA-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 445451.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADD3 | NM_016824.5 | c.*2_*5del | stop_retained_variant, 3_prime_UTR_variant | 15/15 | ENST00000356080.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADD3 | ENST00000356080.9 | c.*2_*5del | stop_retained_variant, 3_prime_UTR_variant | 15/15 | 1 | NM_016824.5 | A1 | ||
ADD3 | ENST00000277900.12 | c.*2_*5del | stop_retained_variant, 3_prime_UTR_variant | 14/14 | 1 | P3 | |||
ADD3 | ENST00000360162.7 | c.*2_*5del | stop_retained_variant, 3_prime_UTR_variant | 14/14 | 1 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000263 AC: 40AN: 152078Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000359 AC: 77AN: 214620Hom.: 0 AF XY: 0.000349 AC XY: 41AN XY: 117378
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GnomAD4 exome AF: 0.000250 AC: 354AN: 1418738Hom.: 0 AF XY: 0.000253 AC XY: 178AN XY: 703960
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GnomAD4 genome ? AF: 0.000263 AC: 40AN: 152078Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74288
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Feb 22, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 17, 2023 | - - |
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at