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GeneBe

5-42800982-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_005410.4(SELENOP):c.884T>C(p.Leu295Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000284 in 1,614,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00028 ( 0 hom. )

Consequence

SELENOP
NM_005410.4 missense

Scores

16

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00600
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)

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0037790537).
BP6
Variant 5-42800982-A-G is Benign according to our data. Variant chr5-42800982-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3159614.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SELENOPNM_005410.4 linkuse as main transcriptc.884T>C p.Leu295Ser missense_variant 5/5 ENST00000514985.6
CCDC152NM_001134848.2 linkuse as main transcriptc.*1201A>G 3_prime_UTR_variant 9/9 ENST00000361970.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SELENOPENST00000514985.6 linkuse as main transcriptc.884T>C p.Leu295Ser missense_variant 5/51 NM_005410.4 P1
CCDC152ENST00000361970.10 linkuse as main transcriptc.*1201A>G 3_prime_UTR_variant 9/91 NM_001134848.2 P1Q4G0S7-1

Frequencies

GnomAD3 genomes
AF:
0.000322
AC:
49
AN:
152248
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000589
Gnomad ASJ
AF:
0.00518
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000250
Gnomad OTH
AF:
0.00191
GnomAD3 exomes
AF:
0.000595
AC:
147
AN:
247064
Hom.:
0
AF XY:
0.000499
AC XY:
67
AN XY:
134258
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000550
Gnomad ASJ exome
AF:
0.00765
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.0000464
Gnomad NFE exome
AF:
0.000334
Gnomad OTH exome
AF:
0.00166
GnomAD4 exome
AF:
0.000280
AC:
409
AN:
1461876
Hom.:
0
Cov.:
33
AF XY:
0.000261
AC XY:
190
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.000418
Gnomad4 AMR exome
AF:
0.000693
Gnomad4 ASJ exome
AF:
0.00624
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000103
Gnomad4 OTH exome
AF:
0.00111
GnomAD4 genome
AF:
0.000322
AC:
49
AN:
152366
Hom.:
0
Cov.:
32
AF XY:
0.000403
AC XY:
30
AN XY:
74528
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000588
Gnomad4 ASJ
AF:
0.00518
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000250
Gnomad4 OTH
AF:
0.00189
Alfa
AF:
0.000524
Hom.:
0
Bravo
AF:
0.000393
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000971
AC:
8
ExAC
AF:
0.000463
AC:
56
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000327
EpiControl
AF:
0.000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsSep 16, 2021This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.53
Cadd
Benign
4.5
Dann
Benign
0.75
DEOGEN2
Benign
0.021
T;T;T;.
Eigen
Benign
-0.77
Eigen_PC
Benign
-0.81
FATHMM_MKL
Benign
0.037
N
MetaRNN
Benign
0.0038
T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
-0.69
N;N;N;.
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Benign
0.26
T
PROVEAN
Benign
1.1
N;N;N;N
REVEL
Benign
0.043
Sift
Benign
0.92
T;T;T;T
Sift4G
Benign
0.60
T;T;T;.
MVP
0.12
MPC
0.37
ClinPred
0.0089
T
GERP RS
-1.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.026

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs202040224; hg19: chr5-42801084; API