chr10-13329705-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3
The NM_012247.5(SEPHS1):c.644T>A(p.Leu215Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000482 in 1,451,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
SEPHS1
NM_012247.5 missense
NM_012247.5 missense
Scores
3
12
4
Clinical Significance
Conservation
PhyloP100: 9.31
Genes affected
SEPHS1 (HGNC:19685): (selenophosphate synthetase 1) This gene encodes an enzyme that synthesizes selenophosphate from selenide and ATP. Selenophosphate is the selenium donor used to synthesize selenocysteine, which is co-translationally incorporated into selenoproteins at in-frame UGA codons. [provided by RefSeq, Sep 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, SEPHS1
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.818
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEPHS1 | NM_012247.5 | c.644T>A | p.Leu215Gln | missense_variant | 6/9 | ENST00000327347.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEPHS1 | ENST00000327347.10 | c.644T>A | p.Leu215Gln | missense_variant | 6/9 | 1 | NM_012247.5 | P1 | |
SEPHS1 | ENST00000545675.5 | c.443T>A | p.Leu148Gln | missense_variant | 5/8 | 1 | |||
SEPHS1 | ENST00000378614.8 | c.644T>A | p.Leu215Gln | missense_variant | 6/8 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.00000427 AC: 1AN: 234138Hom.: 0 AF XY: 0.00000793 AC XY: 1AN XY: 126026
GnomAD3 exomes
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GnomAD4 exome AF: 0.00000482 AC: 7AN: 1451386Hom.: 0 Cov.: 30 AF XY: 0.00000555 AC XY: 4AN XY: 720798
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
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ExAC
?
AF:
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2
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 17, 2023 | The c.644T>A (p.L215Q) alteration is located in exon 6 (coding exon 5) of the SEPHS1 gene. This alteration results from a T to A substitution at nucleotide position 644, causing the leucine (L) at amino acid position 215 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;D
REVEL
Uncertain
Sift
Uncertain
D;.;D
Sift4G
Uncertain
T;T;D
Polyphen
P;.;.
Vest4
MutPred
Loss of helix (P = 0.028);.;Loss of helix (P = 0.028);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at