rs1057518887

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The NM_016955.4(SEPSECS):​c.388+5G>A variant causes a splice region, intron change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 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_region, intron

Scores

2
Splicing: ADA: 0.9997
2

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 6.58
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
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 Protein UniProt
SEPSECSNM_016955.4 linkuse as main transcriptc.388+5G>A splice_region_variant, intron_variant ENST00000382103.7 NP_058651.3 Q9HD40-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SEPSECSENST00000382103.7 linkuse as main transcriptc.388+5G>A splice_region_variant, intron_variant 1 NM_016955.4 ENSP00000371535.2 Q9HD40-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1288868
Hom.:
0
Cov.:
20
AF XY:
0.00
AC XY:
0
AN XY:
650242
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
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 submitterclinical testingCentre for Mendelian Genomics, University Medical Centre LjubljanaSep 06, 2014- -
Pontocerebellar hypoplasia type 2D Pathogenic:1
Likely pathogenic, criteria provided, single submitterclinical testingCentre for Mendelian Genomics, University Medical Centre LjubljanaJan 01, 2016This variant was classified as: Likely pathogenic. This variant was detected in homozygous state. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.31
CADD
Benign
23
DANN
Benign
0.90

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
1.0
dbscSNV1_RF
Pathogenic
0.93
SpliceAI score (max)
0.60
Details are displayed if max score is > 0.2
DS_DL_spliceai
0.60
Position offset: 5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1057518887; hg19: chr4-25158473; API