NM_005410.4:c.605C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005410.4(SELENOP):​c.605C>T​(p.Ser202Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000853 in 1,614,022 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00060 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00088 ( 2 hom. )

Consequence

SELENOP
NM_005410.4 missense

Scores

1
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.249
Variant links:
Genes affected
SELENOP (HGNC:10751): (selenoprotein P) This gene encodes a selenoprotein that is predominantly expressed in the liver and secreted into the plasma. This selenoprotein is unique in that it contains multiple selenocysteine (Sec) residues per polypeptide (10 in human), and accounts for most of the selenium in plasma. It has been implicated as an extracellular antioxidant, and in the transport of selenium to extra-hepatic tissues via apolipoprotein E receptor-2 (apoER2). Mice lacking this gene exhibit neurological dysfunction, suggesting its importance in normal brain function. 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 mRNA for this selenoprotein contains two SECIS elements. The use of alternative polyadenylation sites, one located in between the two SECIS elements, results in two populations of mRNAs containing either both (predominant) or just the upstream SECIS element (PMID:27881738). Alternatively spliced transcript variants have also been found for this gene. [provided by RefSeq, Oct 2018]
CCDC152 (HGNC:34438): (coiled-coil domain containing 152)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0088581145).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SELENOPNM_005410.4 linkc.605C>T p.Ser202Leu missense_variant Exon 5 of 5 ENST00000514985.6 NP_005401.3
CCDC152NM_001134848.2 linkc.*1480G>A 3_prime_UTR_variant Exon 9 of 9 ENST00000361970.10 NP_001128320.1 Q4G0S7-1A0A024R043

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SELENOPENST00000514985.6 linkc.605C>T p.Ser202Leu missense_variant Exon 5 of 5 1 NM_005410.4 ENSP00000420939.1 P49908
CCDC152ENST00000361970.10 linkc.*1480G>A 3_prime_UTR_variant Exon 9 of 9 1 NM_001134848.2 ENSP00000354888.5 Q4G0S7-1

Frequencies

GnomAD3 genomes
AF:
0.000605
AC:
92
AN:
152134
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000193
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000188
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00119
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000539
AC:
134
AN:
248390
AF XY:
0.000541
show subpopulations
Gnomad AFR exome
AF:
0.000129
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000556
Gnomad FIN exome
AF:
0.000139
Gnomad NFE exome
AF:
0.00111
Gnomad OTH exome
AF:
0.000331
GnomAD4 exome
AF:
0.000879
AC:
1285
AN:
1461770
Hom.:
2
Cov.:
33
AF XY:
0.000811
AC XY:
590
AN XY:
727190
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
AC:
4
AN:
33480
Gnomad4 AMR exome
AF:
0.00
AC:
0
AN:
44724
Gnomad4 ASJ exome
AF:
0.00
AC:
0
AN:
26136
Gnomad4 EAS exome
AF:
0.000101
AC:
4
AN:
39698
Gnomad4 SAS exome
AF:
0.0000116
AC:
1
AN:
86252
Gnomad4 FIN exome
AF:
0.000206
AC:
11
AN:
53396
Gnomad4 NFE exome
AF:
0.00110
AC:
1224
AN:
1111920
Gnomad4 Remaining exome
AF:
0.000662
AC:
40
AN:
60396
Heterozygous variant carriers
0
66
133
199
266
332
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Exome Het
Exome Hom
Variant carriers
0
48
96
144
192
240
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000604
AC:
92
AN:
152252
Hom.:
0
Cov.:
32
AF XY:
0.000551
AC XY:
41
AN XY:
74444
show subpopulations
Gnomad4 AFR
AF:
0.000193
AC:
0.000192521
AN:
0.000192521
Gnomad4 AMR
AF:
0.0000654
AC:
0.000065368
AN:
0.000065368
Gnomad4 ASJ
AF:
0.00
AC:
0
AN:
0
Gnomad4 EAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 SAS
AF:
0.00
AC:
0
AN:
0
Gnomad4 FIN
AF:
0.000188
AC:
0.000188288
AN:
0.000188288
Gnomad4 NFE
AF:
0.00119
AC:
0.00119114
AN:
0.00119114
Gnomad4 OTH
AF:
0.00
AC:
0
AN:
0
Heterozygous variant carriers
0
5
11
16
22
27
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.000834
Hom.:
0
Bravo
AF:
0.000552
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.000476
AC:
2
ESP6500EA
AF:
0.000943
AC:
8
ExAC
AF:
0.000644
AC:
78
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000872
EpiControl
AF:
0.000711

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 31, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.605C>T (p.S202L) alteration is located in exon 5 (coding exon 4) of the SEPP1 gene. This alteration results from a C to T substitution at nucleotide position 605, causing the serine (S) at amino acid position 202 to be replaced by a leucine (L). 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
-0.64
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
7.3
DANN
Benign
0.80
Eigen
Benign
-0.98
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.10
N
MetaRNN
Benign
0.0089
T
Sift4G
Uncertain
0.045
D
MVP
0.067
ClinPred
0.0085
T
GERP RS
-1.0
Varity_R
0.035
Mutation Taster
=100/0
polymorphism

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: rs72563758; hg19: chr5-42801363; COSMIC: COSV62794367; COSMIC: COSV62794367; API