chr15-64974736-A-G
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_016630.7(SPG21):āc.318T>Cā(p.Phe106=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000616 in 1,614,180 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0036 ( 7 hom., cov: 32)
Exomes š: 0.00030 ( 2 hom. )
Consequence
SPG21
NM_016630.7 synonymous
NM_016630.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.00
Genes affected
SPG21 (HGNC:20373): (SPG21 abhydrolase domain containing, maspardin) The protein encoded by this gene binds to the hydrophobic C-terminal amino acids of CD4 which are involved in repression of T cell activation. The interaction with CD4 is mediated by the noncatalytic alpha/beta hydrolase fold domain of this protein. It is thus proposed that this gene product modulates the stimulatory activity of CD4. Mutations in this gene are associated with autosomal recessive spastic paraplegia 21 (SPG21), also known as mast syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 15-64974736-A-G is Benign according to our data. Variant chr15-64974736-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 415528.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=2 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPG21 | NM_016630.7 | c.318T>C | p.Phe106= | synonymous_variant | 5/9 | ENST00000204566.7 | |
SPG21 | NM_001127889.5 | c.318T>C | p.Phe106= | synonymous_variant | 5/9 | ||
SPG21 | NM_001127890.5 | c.237T>C | p.Phe79= | synonymous_variant | 4/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPG21 | ENST00000204566.7 | c.318T>C | p.Phe106= | synonymous_variant | 5/9 | 1 | NM_016630.7 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00362 AC: 551AN: 152204Hom.: 7 Cov.: 32
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GnomAD3 exomes AF: 0.000796 AC: 200AN: 251300Hom.: 0 AF XY: 0.000523 AC XY: 71AN XY: 135876
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GnomAD4 exome AF: 0.000304 AC: 444AN: 1461858Hom.: 2 Cov.: 31 AF XY: 0.000245 AC XY: 178AN XY: 727224
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GnomAD4 genome AF: 0.00362 AC: 551AN: 152322Hom.: 7 Cov.: 32 AF XY: 0.00349 AC XY: 260AN XY: 74486
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 22, 2021 | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 29, 2016 | - - |
Mast syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 25, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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