chr20-3471319-C-CGCT
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP3BS2
The NM_139321.3(ATRN):c.230_232dup(p.Leu77dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000466 in 1,481,214 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000046 ( 0 hom. )
Consequence
ATRN
NM_139321.3 inframe_insertion
NM_139321.3 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.02
Genes affected
ATRN (HGNC:885): (attractin) This gene encodes both membrane-bound and secreted protein isoforms. A membrane-bound isoform exhibits sequence similarity with the mouse mahogany protein, a receptor involved in controlling obesity. A secreted isoform is involved in the initial immune cell clustering during inflammatory responses that may regulate the chemotactic activity of chemokines. [provided by RefSeq, Apr 2016]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
BP3
?
Nonframeshift variant in repetitive region in NM_139321.3
BS2
?
High AC in GnomAd at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ATRN | NM_139321.3 | c.230_232dup | p.Leu77dup | inframe_insertion | 1/29 | ENST00000262919.10 | |
ATRN | NM_001323332.2 | c.230_232dup | p.Leu77dup | inframe_insertion | 1/26 | ||
ATRN | NM_139322.4 | c.230_232dup | p.Leu77dup | inframe_insertion | 1/25 | ||
ATRN | NM_001207047.3 | c.62+203_62+205dup | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ATRN | ENST00000262919.10 | c.230_232dup | p.Leu77dup | inframe_insertion | 1/29 | 5 | NM_139321.3 | P2 | |
ATRN | ENST00000446916.2 | c.230_232dup | p.Leu77dup | inframe_insertion | 1/25 | 1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152068Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000587 AC: 4AN: 68158Hom.: 0 AF XY: 0.0000765 AC XY: 3AN XY: 39226
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GnomAD4 exome AF: 0.0000459 AC: 61AN: 1329038Hom.: 0 Cov.: 32 AF XY: 0.0000550 AC XY: 36AN XY: 655008
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152176Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74396
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | This variant, c.230_232dup, results in the insertion of 1 amino acid(s) of the ATRN protein (p.Leu77dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs773492637, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with ATRN-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at