rs922687230

Variant names:

• chr3-53888462-C-T
• rs922687230
• NM_021237.5:c.41G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_021237.5(SELENOK):​c.41G>A​(p.Ser14Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000807 in 1,611,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SELENOK NM_021237.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0950
• Publications: 0 publications found

Genes affected

SELENOK (HGNC:30394): (selenoprotein K) The protein encoded by this gene belongs to the selenoprotein K family. It is a transmembrane protein that is localized in the endoplasmic reticulum (ER), and is involved in ER-associated degradation (ERAD) of misfolded, glycosylated proteins. It also has a role in the protection of cells from ER stress-induced apoptosis. Knockout studies in mice show the importance of this gene in promoting Ca(2+) flux in immune cells and mounting effective immune response. 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. Pseudogenes of this locus have been identified on chromosomes 6 and 19.[provided by RefSeq, Aug 2017]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10133374).
• BP6: Variant 3-53888462-C-T is Benign according to our data. Variant chr3-53888462-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3159522.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021237.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOK	NM_021237.5	MANE Select	c.41G>A	p.Ser14Asn	missense	Exon 2 of 5	NP_067060.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOK	ENST00000495461.6	TSL:1 MANE Select	c.41G>A	p.Ser14Asn	missense	Exon 2 of 5	ENSP00000418813.1	Q9Y6D0
	SELENOK	ENST00000485414.1	TSL:5	n.273G>A		non_coding_transcript_exon	Exon 3 of 3
	SELENOK	ENST00000487571.1	TSL:2	n.108G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152220 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 247884 AF XY: 0.00

Gnomad AFR exome AF: 0.0000641

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000480 AC: 7 AN: 1458948 Hom.: 0 Cov.: 29 AF XY: 0.00000276 AC XY: 2 AN XY: 725940

African (AFR) AF: 0.0000897 AC: 3 AN: 33454

American (AMR) AF: 0.0000224 AC: 1 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111150

Other (OTH) AF: 0.0000497 AC: 3 AN: 60348

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152220 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74362

African (AFR) AF: 0.0000482 AC: 2 AN: 41466

American (AMR) AF: 0.000262 AC: 4 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000106

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	14
DANN	Benign	0.91
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.095
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.11
Sift	Benign	0.24	T
Sift4G	Benign	0.16	T
Polyphen		0.0	B
Vest4		0.20
MutPred		0.15		Loss of disorder (P = 0.0685)
MVP		0.18
MPC		0.051
ClinPred		0.29	T
GERP RS		1.4
Varity_R		0.035
Mutation Taster		=87/13	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

Other links and lift over

dbSNP: rs922687230; hg19: chr3-53922489;