dbSNP rs34423002: SEPSECS:c.115-8_115-4delTTTTT (chr4-25159110-TAAAAA-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_016955.4(SEPSECS):c.115-8_115-4delTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: not found (cov: 26)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SEPSECS
NM_016955.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.13

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: PanelApp Australia, Broad Center for Mendelian Genomics, 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

SEPSECS links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_016955.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016955.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPSECS	NM_016955.4	MANE Select	c.115-8_115-4delTTTTT		splice_region intron	N/A	NP_058651.3	Q9HD40-1
	SEPSECS	NM_001410714.1		c.370-8_370-4delTTTTT		splice_region intron	N/A	NP_001397643.1	A0A7P0TA23

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SEPSECS	ENST00000382103.7	TSL:1 MANE Select	c.115-8_115-4delTTTTT	splice_region intron	N/A	ENSP00000371535.2	Q9HD40-1
SEPSECS	ENST00000358971.7	TSL:1	n.252-8_252-4delTTTTT	splice_region intron	N/A	ENSP00000351857.3	J3KP25
SEPSECS	ENST00000514585.5	TSL:1	n.114+1141_114+1145delTTTTT	intron	N/A	ENSP00000421880.1	Q9HD40-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1321394

Hom.:

AF XY:

0.00

AC XY:

AN XY:

657020

African (AFR)

AF:

0.00

AC:

AN:

27882

American (AMR)

AF:

0.00

AC:

AN:

29552

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23180

East Asian (EAS)

AF:

0.00

AC:

AN:

37076

South Asian (SAS)

AF:

0.00

AC:

AN:

72304

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48144

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5258

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1023236

Other (OTH)

AF:

0.00

AC:

AN:

54762

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.1

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over