Genetic Variant SEPSECS:c.115-5_115-4dupTT (chr4-25159110-T-TAA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_016955.4(SEPSECS):c.115-5_115-4dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0266 in 1,419,864 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: 𝑓 0.00096 ( 0 hom., cov: 26)

Exomes 𝑓: 0.029 ( 0 hom. )

Consequence

SEPSECS
NM_016955.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.42

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPSECS	NM_016955.4 link	c.115-5_115-4dupTT		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
SEPSECS	ENST00000382103.7 link	c.115-5_115-4dupTT		splice_region_variant, intron_variant	Intron 1 of 10	1	NM_016955.4	ENSP00000371535.2		Q9HD40-1

Frequencies

GnomAD3 genomes

AF:

0.000907

AC:

128

AN:

141090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000284

Gnomad ASJ

AF:

0.000299

Gnomad EAS

AF:

0.00304

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00120

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000531

Gnomad OTH

AF:

0.00208

GnomAD4 exome

AF:

0.0294

AC:

37592

AN:

1278692

Hom.:

Cov.:

AF XY:

0.0293

AC XY:

18605

AN XY:

635790

show subpopulations

Gnomad4 AFR exome

AF:

0.0618

Gnomad4 AMR exome

AF:

0.0281

Gnomad4 ASJ exome

AF:

0.0304

Gnomad4 EAS exome

AF:

0.0259

Gnomad4 SAS exome

AF:

0.0356

Gnomad4 FIN exome

AF:

0.0127

Gnomad4 NFE exome

AF:

0.0289

Gnomad4 OTH exome

AF:

0.0320

GnomAD4 genome

AF:

0.000956

AC:

135

AN:

141172

Hom.:

Cov.:

AF XY:

0.000950

AC XY:

AN XY:

68406

show subpopulations

Gnomad4 AFR

AF:

0.00169

Gnomad4 AMR

AF:

0.000284

Gnomad4 ASJ

AF:

0.000299

Gnomad4 EAS

AF:

0.00305

Gnomad4 SAS

AF:

0.000227

Gnomad4 FIN

AF:

0.00120

Gnomad4 NFE

AF:

0.000531

Gnomad4 OTH

AF:

0.00206

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

4-25159110-TAAAAA-TAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over