22-50201121-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000380903.7(SELENOO):​c.85C>T​(p.Pro29Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,334,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000093 ( 0 hom. )

Consequence

SELENOO
ENST00000380903.7 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.594
Variant links:
Genes affected
SELENOO (HGNC:30395): (selenoprotein O) This gene encodes a selenoprotein that is localized to the mitochondria. It is the largest mammalian 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. The exact function of this selenoprotein is not known, but it is thought to have redox activity. [provided by RefSeq, Dec 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06535223).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SELENOONM_031454.2 linkuse as main transcriptc.85C>T p.Pro29Ser missense_variant 1/9 ENST00000380903.7 NP_113642.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SELENOOENST00000380903.7 linkuse as main transcriptc.85C>T p.Pro29Ser missense_variant 1/91 NM_031454.2 ENSP00000370288 P1

Frequencies

GnomAD3 genomes
AF:
0.0000264
AC:
4
AN:
151748
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000589
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000930
AC:
11
AN:
1182498
Hom.:
0
Cov.:
35
AF XY:
0.00000520
AC XY:
3
AN XY:
577450
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000113
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000264
AC:
4
AN:
151748
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74132
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000589
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

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 submitterclinical testingAmbry GeneticsFeb 28, 2024The c.85C>T (p.P29S) alteration is located in exon 1 (coding exon 1) of the SELO gene. This alteration results from a C to T substitution at nucleotide position 85, causing the proline (P) at amino acid position 29 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
0.65
DANN
Benign
0.82
DEOGEN2
Benign
0.010
.;T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.031
N
LIST_S2
Benign
0.40
T;T
MetaRNN
Benign
0.065
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.55
.;N
MutationTaster
Benign
1.0
N
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
0.58
.;N
REVEL
Benign
0.015
Sift
Benign
0.58
.;T
Sift4G
Benign
1.0
T;T
Polyphen
0.0010
.;B
Vest4
0.079
MutPred
0.22
Gain of phosphorylation at P29 (P = 0.0101);Gain of phosphorylation at P29 (P = 0.0101);
MVP
0.13
MPC
0.096
ClinPred
0.13
T
GERP RS
-3.7
Varity_R
0.036

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs1263493785; hg19: chr22-50639550; API