chr1-86863482-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004261.5(SELENOF):​c.490C>T​(p.Arg164Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,611,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. R164H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

SELENOF
NM_004261.5 missense

Scores

3
3
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.00
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1948241).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SELENOFNM_004261.5 linkuse as main transcriptc.490C>T p.Arg164Cys missense_variant 5/5 ENST00000331835.10
SELENOFNM_203341.3 linkuse as main transcriptc.*65C>T 3_prime_UTR_variant 4/4
SELENOFNR_144512.1 linkuse as main transcriptn.567C>T non_coding_transcript_exon_variant 5/5
SELENOFNR_144513.1 linkuse as main transcriptn.551C>T 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.490C>T p.Arg164Cys missense_variant 5/51 NM_004261.5 P1O60613-1

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152108
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.000289
Gnomad EAS
AF:
0.00115
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000650
AC:
16
AN:
246182
Hom.:
0
AF XY:
0.0000749
AC XY:
10
AN XY:
133566
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000100
Gnomad EAS exome
AF:
0.000618
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000268
Gnomad OTH exome
AF:
0.000168
GnomAD4 exome
AF:
0.0000260
AC:
38
AN:
1458918
Hom.:
0
Cov.:
30
AF XY:
0.0000303
AC XY:
22
AN XY:
725694
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000345
Gnomad4 EAS exome
AF:
0.000253
Gnomad4 SAS exome
AF:
0.0000350
Gnomad4 FIN exome
AF:
0.0000188
Gnomad4 NFE exome
AF:
0.00000990
Gnomad4 OTH exome
AF:
0.0000664
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152226
Hom.:
0
Cov.:
32
AF XY:
0.0000940
AC XY:
7
AN XY:
74434
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.000289
Gnomad4 EAS
AF:
0.00116
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000103
Hom.:
0
Bravo
AF:
0.0000491
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000122
AC:
1
ExAC
AF:
0.0000497
AC:
6

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 GeneticsJan 31, 2022The c.490C>T (p.R164C) alteration is located in exon 5 (coding exon 5) of the SEP15 gene. This alteration results from a C to T substitution at nucleotide position 490, causing the arginine (R) at amino acid position 164 to be replaced by a cysteine (C). 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
-0.28
T
BayesDel_noAF
Benign
-0.17
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.042
.;T
Eigen
Pathogenic
0.77
Eigen_PC
Pathogenic
0.81
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.76
T;T
MetaRNN
Benign
0.19
T;T
MetaSVM
Benign
-0.63
T
MutationTaster
Benign
1.0
D;D;D
REVEL
Uncertain
0.30
Sift4G
Uncertain
0.0020
D;D
Vest4
0.63
MVP
0.28
MPC
0.86
ClinPred
0.46
T
GERP RS
6.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.21

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: rs148099140; hg19: chr1-87329165; API