rs1057518887
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_ModeratePP5_Moderate
The NM_016955.4(SEPSECS):c.388+5G>A variant causes a splice donor 5th base, intron change. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SEPSECS
NM_016955.4 splice_donor_5th_base, intron
NM_016955.4 splice_donor_5th_base, intron
Scores
2
Splicing: ADA: 0.9997
2
Clinical Significance
Conservation
PhyloP100: 6.58
Genes affected
SEPSECS (HGNC:30605): (Sep (O-phosphoserine) tRNA:Sec (selenocysteine) tRNA synthase) The amino acid selenocysteine is the only amino acid that does not have its own tRNA synthetase. Instead, this amino acid is synthesized on its cognate tRNA in a three step process. The protein encoded by this gene catalyzes the third step in the process, the conversion of O-phosphoseryl-tRNA(Sec) to selenocysteinyl-tRNA(Sec).[provided by RefSeq, Mar 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
?
Variant 4-25156851-C-T is Pathogenic according to our data. Variant chr4-25156851-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 374085.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-25156851-C-T is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEPSECS | NM_016955.4 | c.388+5G>A | splice_donor_5th_base_variant, intron_variant | ENST00000382103.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEPSECS | ENST00000382103.7 | c.388+5G>A | splice_donor_5th_base_variant, intron_variant | 1 | NM_016955.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 1288868Hom.: 0 Cov.: 20 AF XY: 0.00 AC XY: 0AN XY: 650242
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
AC:
0
AN:
1288868
Hom.:
Cov.:
20
AF XY:
AC XY:
0
AN XY:
650242
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Kyphosis;C0036572:Seizure;C1837397:Severe global developmental delay;C1855330:Cerebral hypoplasia;C1858025:Spinal rigidity;C5231391:Congenital cerebellar hypoplasia;C5779613:Arthrogryposis multiplex congenita Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Sep 06, 2014 | - - |
Pontocerebellar hypoplasia type 2D Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Jan 01, 2016 | This variant was classified as: Likely pathogenic. This variant was detected in homozygous state. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: 5
Find out detailed SpliceAI scores and Pangolin per-transcript scores at