chr1-39084257-A-ATGTCGGAGTGAGCGGTCT
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM4BS2
The ENST00000567887.5(MACF1):c.54_71dup(p.Cys20_Ser25dup) variant causes a inframe insertion change. The variant allele was found at a frequency of 0.000158 in 152,224 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00017 ( 1 hom. )
Failed GnomAD Quality Control
Consequence
MACF1
ENST00000567887.5 inframe_insertion
ENST00000567887.5 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.15
Genes affected
MACF1 (HGNC:13664): (microtubule actin crosslinking factor 1) This gene encodes a large protein containing numerous spectrin and leucine-rich repeat (LRR) domains. The encoded protein is a member of a family of proteins that form bridges between different cytoskeletal elements. This protein facilitates actin-microtubule interactions at the cell periphery and couples the microtubule network to cellular junctions. Alternative splicing results in multiple transcript variants, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in ENST00000567887.5.
BS2
High AC in GnomAd4 at 24 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MACF1 | NM_012090.5 | c.54_71dup | p.Cys20_Ser25dup | inframe_insertion | 1/93 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MACF1 | ENST00000361689.7 | c.54_71dup | p.Cys20_Ser25dup | inframe_insertion | 2/94 | 5 | |||
MACF1 | ENST00000372915.8 | c.54_71dup | p.Cys20_Ser25dup | inframe_insertion | 1/96 | 5 | P1 | ||
MACF1 | ENST00000484793.5 | c.54_71dup | p.Cys20_Ser25dup | inframe_insertion | 3/4 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000158 AC: 24AN: 152106Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000195 AC: 49AN: 251130Hom.: 0 AF XY: 0.000177 AC XY: 24AN XY: 135770
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000167 AC: 244AN: 1460624Hom.: 1 Cov.: 30 AF XY: 0.000180 AC XY: 131AN XY: 726692
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Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome AF: 0.000158 AC: 24AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74432
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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 | Nov 28, 2023 | This variant, c.54_71dup, results in the insertion of 6 amino acid(s) of the MACF1 protein (p.Cys20_Ser25dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs758220322, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with MACF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2186705). 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. - |
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at