rs142334011
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_002361.4(MAG):c.228G>A(p.Ser76Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0024 in 1,613,682 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0019 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0025 ( 16 hom. )
Consequence
MAG
NM_002361.4 synonymous
NM_002361.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.81
Genes affected
MAG (HGNC:6783): (myelin associated glycoprotein) The protein encoded by this gene is a type I membrane protein and member of the immunoglobulin superfamily. It is thought to be involved in the process of myelination. It is a lectin that binds to sialylated glycoconjugates and mediates certain myelin-neuron cell-cell interactions. Three alternatively spliced transcripts encoding different isoforms have been described for this gene. [provided by RefSeq, Nov 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
Variant 19-35295794-G-A is Benign according to our data. Variant chr19-35295794-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 475607.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.81 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00193 (293/152084) while in subpopulation SAS AF= 0.00603 (29/4812). AF 95% confidence interval is 0.00431. There are 2 homozygotes in gnomad4. There are 147 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MAG | NM_002361.4 | c.228G>A | p.Ser76Ser | synonymous_variant | 4/11 | ENST00000392213.8 | NP_002352.1 | |
MAG | NM_001199216.2 | c.153G>A | p.Ser51Ser | synonymous_variant | 4/11 | NP_001186145.1 | ||
MAG | NM_080600.3 | c.228G>A | p.Ser76Ser | synonymous_variant | 4/12 | NP_542167.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MAG | ENST00000392213.8 | c.228G>A | p.Ser76Ser | synonymous_variant | 4/11 | 1 | NM_002361.4 | ENSP00000376048.2 |
Frequencies
GnomAD3 genomes AF: 0.00195 AC: 296AN: 151966Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.00257 AC: 645AN: 250946Hom.: 6 AF XY: 0.00303 AC XY: 411AN XY: 135704
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GnomAD4 exome AF: 0.00245 AC: 3587AN: 1461598Hom.: 16 Cov.: 31 AF XY: 0.00267 AC XY: 1945AN XY: 727130
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GnomAD4 genome AF: 0.00193 AC: 293AN: 152084Hom.: 2 Cov.: 32 AF XY: 0.00198 AC XY: 147AN XY: 74342
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2024 | MAG: BP4, BP7, BS2 - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Hereditary spastic paraplegia 75 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 30, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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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