chr4-25159110-TAA-T

Variant summary

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

The NM_016955.4(SEPSECS):​c.115-5_115-4delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000706 in 1,456,956 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000057 ( 0 hom., cov: 26)
Exomes 𝑓: 0.00078 ( 0 hom. )

Consequence

SEPSECS
NM_016955.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.13

Publications

5 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 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SEPSECSNM_016955.4 linkc.115-5_115-4delTT 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.115-5_115-4delTT splice_region_variant, intron_variant Intron 1 of 10 1 NM_016955.4 ENSP00000371535.2 Q9HD40-1

Frequencies

GnomAD3 genomes
AF:
0.0000567
AC:
8
AN:
141122
Hom.:
0
Cov.:
26
show subpopulations
Gnomad AFR
AF:
0.000103
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000358
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000156
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00104
AC:
133
AN:
128440
AF XY:
0.00108
show subpopulations
Gnomad AFR exome
AF:
0.00159
Gnomad AMR exome
AF:
0.00147
Gnomad ASJ exome
AF:
0.00106
Gnomad EAS exome
AF:
0.000669
Gnomad FIN exome
AF:
0.00105
Gnomad NFE exome
AF:
0.00103
Gnomad OTH exome
AF:
0.000640
GnomAD4 exome
AF:
0.000775
AC:
1020
AN:
1315834
Hom.:
0
AF XY:
0.000784
AC XY:
513
AN XY:
654306
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00115
AC:
32
AN:
27808
American (AMR)
AF:
0.00122
AC:
36
AN:
29410
Ashkenazi Jewish (ASJ)
AF:
0.000736
AC:
17
AN:
23104
East Asian (EAS)
AF:
0.000270
AC:
10
AN:
37014
South Asian (SAS)
AF:
0.000903
AC:
65
AN:
71998
European-Finnish (FIN)
AF:
0.000312
AC:
15
AN:
48016
Middle Eastern (MID)
AF:
0.000761
AC:
4
AN:
5254
European-Non Finnish (NFE)
AF:
0.000778
AC:
793
AN:
1018648
Other (OTH)
AF:
0.000879
AC:
48
AN:
54582
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.247
Heterozygous variant carriers
0
150
300
450
600
750
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
32
64
96
128
160
<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
AF:
0.0000567
AC:
8
AN:
141122
Hom.:
0
Cov.:
26
AF XY:
0.0000878
AC XY:
6
AN XY:
68324
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.000103
AC:
4
AN:
38892
American (AMR)
AF:
0.00
AC:
0
AN:
14066
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3340
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4930
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4426
European-Finnish (FIN)
AF:
0.000358
AC:
3
AN:
8378
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
308
European-Non Finnish (NFE)
AF:
0.0000156
AC:
1
AN:
63990
Other (OTH)
AF:
0.00
AC:
0
AN:
1922
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 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: 0.363
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome 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
Alfa
AF:
0.00
Hom.:
12

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
3.1
Mutation Taster
=96/4
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
Details are displayed if max score is > 0.2

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