chr1-86868084-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_004261.5(SELENOF):āc.335A>Gā(p.Lys112Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000197 in 152,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 32)
Exomes š: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
SELENOF
NM_004261.5 missense
NM_004261.5 missense
Scores
1
2
11
Clinical Significance
Conservation
PhyloP100: 5.93
Genes affected
SELENOF (HGNC:17705): (selenoprotein F) The protein encoded by this gene belongs to the SEP15/selenoprotein M family. The exact function of this protein is not known; however, it has been found to associate with UDP-glucose:glycoprotein glucosyltransferase (UGTR), an endoplasmic reticulum(ER)-resident protein, which is involved in the quality control of protein folding. The association with UGTR retains this protein in the ER, where it may play a role in protein folding. It has also been suggested to have a role in cancer etiology. This protein is a selenoprotein, containing the rare amino acid selenocysteine (Sec). Sec is encoded by the UGA codon, which normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, designated the Sec insertion sequence (SECIS) element, that is necessary for the recognition of UGA as a Sec codon, rather than as a stop signal. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2016]
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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;
BP4
Computational evidence support a benign effect (MetaRNN=0.270189).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SELENOF | NM_004261.5 | c.335A>G | p.Lys112Arg | missense_variant | 4/5 | ENST00000331835.10 | |
SELENOF | NM_203341.3 | c.317-4479A>G | intron_variant | ||||
SELENOF | NR_144512.1 | n.412A>G | non_coding_transcript_exon_variant | 4/5 | |||
SELENOF | NR_144513.1 | n.396A>G | non_coding_transcript_exon_variant | 4/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SELENOF | ENST00000331835.10 | c.335A>G | p.Lys112Arg | missense_variant | 4/5 | 1 | NM_004261.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152094Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000458 AC: 1AN: 218340Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 119434
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1375148Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 685580
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152094Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74304
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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 | May 23, 2024 | The c.335A>G (p.K112R) alteration is located in exon 4 (coding exon 4) of the SEP15 gene. This alteration results from a A to G substitution at nucleotide position 335, causing the lysine (K) at amino acid position 112 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
REVEL
Benign
Sift4G
Benign
T;T
Vest4
0.41
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
Splicing
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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