rs1371721068

Variant names:

• chr15-101275350-C-A
• rs1371721068
• NM_018445.6:c.223G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-101275350-C-A
• chr15-101275350-C-T

Variant summary

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

The NM_018445.6(SELENOS):​c.223G>T​(p.Val75Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,420,074 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: SELENOS NM_018445.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66

Genes affected

SELENOS (HGNC:30396): (selenoprotein S) This gene encodes a transmembrane protein that is localized in the endoplasmic reticulum (ER). It is involved in the degradation process of misfolded proteins in the ER, and may also have a role in inflammation control. 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. Two additional phylogenetically conserved stem-loop structures (Stem-loop 1 and Stem-loop 2) in the 3' UTR of this mRNA have been shown to function as modulators of Sec insertion. An alternatively spliced transcript variant, lacking the SECIS element and encoding a non-Sec containing shorter isoform, has been described for this gene (PMID:23614019). [provided by RefSeq, Jul 2017]

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
SELENOS	NM_018445.6	c.223G>T	p.Val75Phe	missense_variant	Exon 3 of 6	ENST00000526049.6	NP_060915.2
SELENOS	NM_203472.3	c.223G>T	p.Val75Phe	missense_variant	Exon 3 of 7		NP_982298.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELENOS	ENST00000526049.6	c.223G>T	p.Val75Phe	missense_variant	Exon 3 of 6	1	NM_018445.6	ENSP00000433541.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.04e-7 AC: 1 AN: 1420074 Hom.: 0 Cov.: 30 AF XY: 0.00000142 AC XY: 1 AN XY: 702786

Gnomad4 AFR exome AF: 0.0000307

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T;.;T;.
Eigen	Benign	0.18
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.93	.;.;D;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.51	D;D;D;D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.4	M;.;M;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.0	D;D;D;D
REVEL	Benign	0.24
Sift	Benign	0.073	T;T;T;T
Sift4G	Uncertain	0.0040	D;D;D;.
Polyphen		0.92	P;.;P;.
Vest4		0.71
MutPred		0.71		Loss of MoRF binding (P = 0.0927);.;Loss of MoRF binding (P = 0.0927);.;
MVP		0.28
MPC		0.25
ClinPred		0.98	D
GERP RS		2.9
Varity_R		0.54

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

Other links and lift over

dbSNP: rs1371721068; hg19: chr15-101815555;