chr1-86914090-G-C

Variant summary

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

The NM_004261.5(SELENOF):ā€‹c.22C>Gā€‹(p.Pro8Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,613,782 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P8S) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 32)
Exomes š‘“: 0.000044 ( 0 hom. )

Consequence

SELENOF
NM_004261.5 missense

Scores

15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.349
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 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=0.059986293).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SELENOFNM_004261.5 linkuse as main transcriptc.22C>G p.Pro8Ala missense_variant 1/5 ENST00000331835.10
SELENOFNM_203341.3 linkuse as main transcriptc.22C>G p.Pro8Ala missense_variant 1/4
SELENOFNR_144512.1 linkuse as main transcriptn.161+225C>G intron_variant, non_coding_transcript_variant
SELENOFNR_144513.1 linkuse as main transcriptn.145+343C>G intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SELENOFENST00000331835.10 linkuse as main transcriptc.22C>G p.Pro8Ala missense_variant 1/51 NM_004261.5 P1O60613-1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152084
Hom.:
0
Cov.:
32
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000442
AC:
11
AN:
248978
Hom.:
0
AF XY:
0.0000148
AC XY:
2
AN XY:
135136
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000532
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.0000438
AC:
64
AN:
1461698
Hom.:
0
Cov.:
31
AF XY:
0.0000468
AC XY:
34
AN XY:
727128
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000894
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000495
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152084
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74256
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:
0.0000588
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000604
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.000164
EpiControl
AF:
0.00

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 GeneticsJun 10, 2022The c.22C>G (p.P8A) alteration is located in exon 1 (coding exon 1) of the SEP15 gene. This alteration results from a C to G substitution at nucleotide position 22, causing the proline (P) at amino acid position 8 to be replaced by an alanine (A). 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
-0.40
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
1.5
DANN
Benign
0.61
DEOGEN2
Benign
0.023
.;.;T;.;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.031
N
LIST_S2
Benign
0.68
T;T;T;T;T
M_CAP
Benign
0.0017
T
MetaRNN
Benign
0.060
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.25
T
REVEL
Benign
0.0080
Sift4G
Benign
0.35
T;T;T;T;T
Vest4
0.17
MVP
0.030
MPC
0.18
ClinPred
0.044
T
GERP RS
-2.0
Varity_R
0.044

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: rs377513226; hg19: chr1-87379773; API