1-86863481-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_004261.5(SELENOF):​c.491G>A​(p.Arg164His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000227 in 1,610,794 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R164C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

SELENOF
NM_004261.5 missense

Scores

4
3
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.751

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SELENOFNM_004261.5 linkuse as main transcriptc.491G>A p.Arg164His missense_variant 5/5 ENST00000331835.10
SELENOFNM_203341.3 linkuse as main transcriptc.*66G>A 3_prime_UTR_variant 4/4
SELENOFNR_144512.1 linkuse as main transcriptn.568G>A non_coding_transcript_exon_variant 5/5
SELENOFNR_144513.1 linkuse as main transcriptn.552G>A non_coding_transcript_exon_variant 5/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SELENOFENST00000331835.10 linkuse as main transcriptc.491G>A p.Arg164His missense_variant 5/51 NM_004261.5 P1O60613-1

Frequencies

GnomAD3 genomes
AF:
0.000145
AC:
22
AN:
152154
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
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:
0.000250
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000691
AC:
17
AN:
246002
Hom.:
0
AF XY:
0.0000674
AC XY:
9
AN XY:
133434
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000297
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000562
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000134
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000235
AC:
343
AN:
1458640
Hom.:
0
Cov.:
30
AF XY:
0.000218
AC XY:
158
AN XY:
725550
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
Gnomad4 AMR exome
AF:
0.0000226
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000188
Gnomad4 NFE exome
AF:
0.000280
Gnomad4 OTH exome
AF:
0.000465
GnomAD4 genome
AF:
0.000145
AC:
22
AN:
152154
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
AN XY:
74314
show subpopulations
Gnomad4 AFR
AF:
0.000121
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:
0.000250
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000181
Hom.:
0
Bravo
AF:
0.000178
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000244
AC:
2
ExAC
AF:
0.0000745
AC:
9
EpiCase
AF:
0.000165
EpiControl
AF:
0.000238

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 GeneticsApr 25, 2023The c.491G>A (p.R164H) alteration is located in exon 5 (coding exon 5) of the SEP15 gene. This alteration results from a G to A substitution at nucleotide position 491, causing the arginine (R) at amino acid position 164 to be replaced by a histidine (H). 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
-0.20
T
BayesDel_noAF
Benign
-0.26
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.039
.;T
Eigen
Pathogenic
0.76
Eigen_PC
Pathogenic
0.80
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.71
T;T
MetaRNN
Pathogenic
0.75
D;D
MetaSVM
Benign
-0.52
T
MutationTaster
Benign
1.0
D;D;D
REVEL
Uncertain
0.50
Sift4G
Uncertain
0.020
D;D
Vest4
0.55
MVP
0.37
MPC
0.38
ClinPred
0.87
D
GERP RS
6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.14

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: rs377045272; hg19: chr1-87329164; API