NM_033505.4:c.58-94G>A

Variant names:

• chr2-26364208-G-A
• rs11674089
• NM_033505.4:c.58-94G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_033505.4(SELENOI):​c.58-94G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 908,394 control chromosomes in the GnomAD database, including 50,588 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7190 hom., cov: 30)
  • Exomes 𝑓: 0.33 (43398 hom.)
• Consequence: SELENOI NM_033505.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.69
• Publications: 4 publications found

Genes affected

SELENOI (HGNC:29361): (selenoprotein I) The multi-pass transmembrane protein encoded by this gene belongs to the CDP-alcohol phosphatidyltransferase class-I family. It catalyzes the transfer of phosphoethanolamine from CDP-ethanolamine to diacylglycerol to produce phosphatidylethanolamine, which is involved in the formation and maintenance of vesicular membranes, regulation of lipid metabolism, and protein folding. This protein is a selenoprotein, containing the rare selenocysteine (Sec) amino acid at its active site. 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. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2016]

SELENOI Gene-Disease associations (from GenCC):

• spastic paraplegia 81, autosomal recessive

  Inheritance: AR Classification: STRONG Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BP6: Variant 2-26364208-G-A is Benign according to our data. Variant chr2-26364208-G-A is described in ClinVar as Benign. ClinVar VariationId is 1239310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033505.4. 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
	SELENOI	NM_033505.4	MANE Select	c.58-94G>A		intron	N/A	NP_277040.1
	SELENOI	NR_137633.2		n.148-94G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOI	ENST00000260585.12	TSL:1 MANE Select	c.58-94G>A		intron	N/A	ENSP00000260585.7
	SELENOI	ENST00000447170.1	TSL:5	c.58-94G>A		intron	N/A	ENSP00000391804.1
	SELENOI	ENST00000442141.5	TSL:5	c.-39-94G>A		intron	N/A	ENSP00000415280.1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43462 AN: 151018 Hom.: 7186 Cov.: 30

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.384

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.324

GnomAD4 exome AF: 0.334 AC: 252550 AN: 757262 Hom.: 43398 AF XY: 0.333 AC XY: 132228 AN XY: 396772

African (AFR) AF: 0.104 AC: 1923 AN: 18416

American (AMR) AF: 0.315 AC: 9404 AN: 29868

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 9337 AN: 20432

East Asian (EAS) AF: 0.196 AC: 6023 AN: 30806

South Asian (SAS) AF: 0.299 AC: 18974 AN: 63534

European-Finnish (FIN) AF: 0.414 AC: 15452 AN: 37358

Middle Eastern (MID) AF: 0.326 AC: 1334 AN: 4090

European-Non Finnish (NFE) AF: 0.344 AC: 177890 AN: 516504

Other (OTH) AF: 0.337 AC: 12213 AN: 36254

GnomAD4 genome AF: 0.288 AC: 43462 AN: 151132 Hom.: 7190 Cov.: 30 AF XY: 0.290 AC XY: 21387 AN XY: 73790

African (AFR) AF: 0.115 AC: 4734 AN: 41112

American (AMR) AF: 0.309 AC: 4687 AN: 15152

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1551 AN: 3460

East Asian (EAS) AF: 0.256 AC: 1309 AN: 5122

South Asian (SAS) AF: 0.304 AC: 1451 AN: 4776

European-Finnish (FIN) AF: 0.420 AC: 4378 AN: 10418

Middle Eastern (MID) AF: 0.375 AC: 108 AN: 288

European-Non Finnish (NFE) AF: 0.358 AC: 24271 AN: 67806

Other (OTH) AF: 0.325 AC: 680 AN: 2090

Alfa AF: 0.338 Hom.: 4802

Bravo AF: 0.273

Asia WGS AF: 0.301 AC: 1048 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.096
DANN	Benign	0.62
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs11674089; hg19: chr2-26587076; COSMIC: COSV53143379;