rs564364975

Variant names:

• chr5-42807022-C-G
• NM_005410.4:c.290G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-42807022-C-G
• chr5-42807022-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005410.4(SELENOP):​c.290G>C​(p.Arg97Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,434,104 control chromosomes in the GnomAD database, with no homozygous occurrence. 11/18 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SELENOP NM_005410.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.987

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]

ENSG00000272234 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELENOP	NM_005410.4	c.290G>C	p.Arg97Pro	missense_variant	Exon 3 of 5	ENST00000514985.6	NP_005401.3
SELENOP	NM_001093726.3	c.380G>C	p.Arg127Pro	missense_variant	Exon 4 of 6		NP_001087195.1
SELENOP	NM_001085486.3	c.290G>C	p.Arg97Pro	missense_variant	Exon 4 of 6		NP_001078955.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELENOP	ENST00000514985.6	c.290G>C	p.Arg97Pro	missense_variant	Exon 3 of 5	1	NM_005410.4	ENSP00000420939.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1434104 Hom.: 0 Cov.: 25 AF XY: 0.00000140 AC XY: 1 AN XY: 714980

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000234

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	11
DANN	Benign	0.84
DEOGEN2	Benign	0.27	T;T;T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.55	.;.;T;.;.
MetaRNN	Uncertain	0.45	T;T;T;T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.5	L;L;L;.;.
PrimateAI	Benign	0.22	T
PROVEAN	Uncertain	-3.5	D;D;D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.017	D;D;D;D;T
Sift4G	Benign	0.083	T;T;T;.;.
MutPred		0.67		Loss of MoRF binding (P = 0.002);Loss of MoRF binding (P = 0.002);Loss of MoRF binding (P = 0.002);Loss of MoRF binding (P = 0.002);Loss of MoRF binding (P = 0.002);
MVP		0.030
MPC		0.091
ClinPred		0.23	T
GERP RS		-9.2
Varity_R		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-42807124;