rs1314207581
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_198586.3(NHLRC1):c.882G>T(p.Val294=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
NHLRC1
NM_198586.3 synonymous
NM_198586.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.513
Genes affected
NHLRC1 (HGNC:21576): (NHL repeat containing E3 ubiquitin protein ligase 1) The protein encoded by this gene is a single subunit E3 ubiquitin ligase. Laforin is polyubiquitinated by the encoded protein. Defects in this intronless gene lead to an accumulation of laforin and onset of Lafora disease, also known as progressive myoclonic epilepsy type 2 (EPM2).[provided by RefSeq, Mar 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
?
Variant 6-18121725-C-A is Benign according to our data. Variant chr6-18121725-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 531815.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.513 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NHLRC1 | NM_198586.3 | c.882G>T | p.Val294= | synonymous_variant | 1/1 | ENST00000340650.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NHLRC1 | ENST00000340650.6 | c.882G>T | p.Val294= | synonymous_variant | 1/1 | NM_198586.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250860Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135786
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461752Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727178
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152236Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74374
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Lafora disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
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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