GeneBe

chr4-25159110-T-TAAAAAA

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016955.4(SEPSECS):​c.115-9_115-4dupTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000378 in 1,321,380 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 26)
Exomes 𝑓: 0.0000038 ( 0 hom. )

Consequence

SEPSECS
NM_016955.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.42

Publications

0 publications found
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]
SEPSECS Gene-Disease associations (from GenCC):
  • pontocerebellar hypoplasia type 2D
    Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Broad Center for Mendelian Genomics, PanelApp Australia, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • pontocerebellar hypoplasia type 2
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • progressive cerebello-cerebral atrophy
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SEPSECSNM_016955.4 linkc.115-9_115-4dupTTTTTT splice_region_variant, intron_variant Intron 1 of 10 ENST00000382103.7 NP_058651.3 Q9HD40-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SEPSECSENST00000382103.7 linkc.115-9_115-4dupTTTTTT splice_region_variant, intron_variant Intron 1 of 10 1 NM_016955.4 ENSP00000371535.2 Q9HD40-1

Frequencies

GnomAD3 genomes
Cov.:
26
GnomAD4 exome
AF:
0.00000378
AC:
5
AN:
1321380
Hom.:
0
Cov.:
22
AF XY:
0.00000457
AC XY:
3
AN XY:
657014
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.0000359
AC:
1
AN:
27882
American (AMR)
AF:
0.00
AC:
0
AN:
29554
Ashkenazi Jewish (ASJ)
AF:
0.0000431
AC:
1
AN:
23180
East Asian (EAS)
AF:
0.00
AC:
0
AN:
37076
South Asian (SAS)
AF:
0.00
AC:
0
AN:
72300
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
48144
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5258
European-Non Finnish (NFE)
AF:
0.00000293
AC:
3
AN:
1023222
Other (OTH)
AF:
0.00
AC:
0
AN:
54764
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000001), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.305
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
-2.4

Splicing

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

Publications

Other links and lift over

dbSNP: rs34423002; hg19: chr4-25160732; API