NM_005410.4:c.85A>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_005410.4(SELENOP):c.85A>G(p.Lys29Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,570,408 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0092 ( 22 hom., cov: 31)

Exomes 𝑓: 0.00082 ( 20 hom. )

Consequence

SELENOP
NM_005410.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.737

Publications

3 publications found

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]

SELENOP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004091978).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00923 (1400/151756) while in subpopulation AFR AF = 0.0323 (1336/41356). AF 95% confidence interval is 0.0309. There are 22 homozygotes in GnomAd4. There are 665 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
SELENOP	NM_005410.4 link	c.85A>G	p.Lys29Glu	missense_variant	Exon 2 of 5	ENST00000514985.6	NP_005401.3
SELENOP	NM_001093726.3 link	c.175A>G	p.Lys59Glu	missense_variant	Exon 3 of 6		NP_001087195.1
SELENOP	NM_001085486.3 link	c.85A>G	p.Lys29Glu	missense_variant	Exon 3 of 6		NP_001078955.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELENOP	ENST00000514985.6 link	c.85A>G	p.Lys29Glu	missense_variant	Exon 2 of 5	1	NM_005410.4	ENSP00000420939.1		P49908

Frequencies

GnomAD3 genomes

AF:

0.00922

AC:

1398

AN:

151638

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00315

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:

0.0000736

Gnomad OTH

AF:

0.00529

GnomAD2 exomes

AF:

0.00210

AC:

468

AN:

222620

AF XY:

0.00142

show subpopulations

Gnomad AFR exome

AF:

0.0328

Gnomad AMR exome

AF:

0.000908

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000192

Gnomad OTH exome

AF:

0.000975

GnomAD4 exome

AF:

0.000824

AC:

1169

AN:

1418652

Hom.:

Cov.:

AF XY:

0.000645

AC XY:

455

AN XY:

705584

show subpopulations

African (AFR)

AF:

0.0323

AC:

1007

AN:

31202

American (AMR)

AF:

0.00124

AC:

AN:

39474

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25016

East Asian (EAS)

AF:

0.00

AC:

AN:

36700

South Asian (SAS)

AF:

0.0000501

AC:

AN:

79774

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52678

Middle Eastern (MID)

AF:

0.000543

AC:

AN:

5522

European-Non Finnish (NFE)

AF:

0.0000138

AC:

AN:

1090066

Other (OTH)

AF:

0.00156

AC:

AN:

58220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

143

191

239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.00923

AC:

1400

AN:

151756

Hom.:

Cov.:

AF XY:

0.00896

AC XY:

665

AN XY:

74210

show subpopulations

African (AFR)

AF:

0.0323

AC:

1336

AN:

41356

American (AMR)

AF:

0.00314

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5086

South Asian (SAS)

AF:

0.00

AC:

AN:

4794

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000736

AC:

AN:

67906

Other (OTH)

AF:

0.00523

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

123

185

246

308

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00412

Hom.:

Bravo

AF:

0.0105

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0325

AC:

121

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00278

AC:

336

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.052

T;T;T;.;.;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.48

.;.;T;.;.;.

MetaRNN

Benign

0.0041

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L;L;.;.;.

PhyloP100

0.74

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.27

N;N;N;.;N;N

REVEL

Benign

0.046

Sift

Benign

0.25

T;T;T;.;T;T

Sift4G

Benign

0.11

T;T;T;T;.;.

Vest4

0.18

MVP

0.076

MPC

0.38

ClinPred

0.032

GERP RS

-0.21

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.043

Mutation Taster

=94/6

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over