4-25159110-TAAA-TA

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6

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. Variant has been reported in Lovd as Benign (no stars).

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
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 4-25159110-TAA-T is Benign according to our data. Variant chr4-25159110-TAA-T is described in Lovd as [Benign].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SEPSECSNM_016955.4 linkuse as main transcriptc.115-5_115-4delTT 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.115-5_115-4delTT splice_region_variant, intron_variant 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
GnomAD4 exome
AF:
0.000775
AC:
1020
AN:
1315834
Hom.:
0
AF XY:
0.000784
AC XY:
513
AN XY:
654306
show subpopulations
Gnomad4 AFR exome
AF:
0.00115
Gnomad4 AMR exome
AF:
0.00122
Gnomad4 ASJ exome
AF:
0.000736
Gnomad4 EAS exome
AF:
0.000270
Gnomad4 SAS exome
AF:
0.000903
Gnomad4 FIN exome
AF:
0.000312
Gnomad4 NFE exome
AF:
0.000778
Gnomad4 OTH exome
AF:
0.000879
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
Gnomad4 AFR
AF:
0.000103
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000358
Gnomad4 NFE
AF:
0.0000156
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

LitVar

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

Other links and lift over

dbSNP: rs34423002; hg19: chr4-25160732; API