NM_031454.2:c.105C>G

Variant names:

• chr22-50201141-C-G
• rs528120489
• NM_031454.2:c.105C>G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_031454.2(SELENOO):​c.105C>G​(p.Gly35Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00704 in 1,301,496 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0059 (2 hom., cov: 34)
  • Exomes 𝑓: 0.0072 (30 hom.)
• Consequence: SELENOO NM_031454.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.910
• Publications: 0 publications found

Genes affected

SELENOO (HGNC:30395): (selenoprotein O) This gene encodes a selenoprotein that is localized to the mitochondria. It is the largest mammalian 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. The exact function of this selenoprotein is not known, but it is thought to have redox activity. [provided by RefSeq, Dec 2016]

TRABD-AS1 (HGNC:56049): (TRABD antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 22-50201141-C-G is Benign according to our data. Variant chr22-50201141-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2653367.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.91 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00719 (8263/1149852) while in subpopulation MID AF = 0.0224 (73/3262). AF 95% confidence interval is 0.0183. There are 30 homozygotes in GnomAdExome4. There are 4048 alleles in the male GnomAdExome4 subpopulation. Median coverage is 35. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031454.2. 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
	SELENOO	NM_031454.2	MANE Select	c.105C>G	p.Gly35Gly	synonymous	Exon 1 of 9	NP_113642.1	Q9BVL4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOO	ENST00000380903.7	TSL:1 MANE Select	c.105C>G	p.Gly35Gly	synonymous	Exon 1 of 9	ENSP00000370288.2	Q9BVL4
	TRABD-AS1	ENST00000803400.1		n.83+373G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00589 AC: 893 AN: 151536 Hom.: 2 Cov.: 34

Gnomad AFR AF: 0.00131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00742

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.00683

Gnomad FIN AF: 0.00764

Gnomad MID AF: 0.0192

Gnomad NFE AF: 0.00759

Gnomad OTH AF: 0.00675

GnomAD2 exomes AF: 0.00755 AC: 116 AN: 15360 AF XY: 0.00822

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00456

Gnomad ASJ exome AF: 0.0224

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00962

Gnomad NFE exome AF: 0.00543

Gnomad OTH exome AF: 0.00493

GnomAD4 exome AF: 0.00719 AC: 8263 AN: 1149852 Hom.: 30 Cov.: 35 AF XY: 0.00726 AC XY: 4048 AN XY: 557582

African (AFR) AF: 0.00110 AC: 25 AN: 22786

American (AMR) AF: 0.00475 AC: 51 AN: 10734

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 335 AN: 16594

East Asian (EAS) AF: 0.0000380 AC: 1 AN: 26302

South Asian (SAS) AF: 0.00652 AC: 261 AN: 40038

European-Finnish (FIN) AF: 0.00665 AC: 166 AN: 24972

Middle Eastern (MID) AF: 0.0224 AC: 73 AN: 3262

European-Non Finnish (NFE) AF: 0.00731 AC: 7016 AN: 959480

Other (OTH) AF: 0.00733 AC: 335 AN: 45684

GnomAD4 genome AF: 0.00590 AC: 894 AN: 151644 Hom.: 2 Cov.: 34 AF XY: 0.00593 AC XY: 440 AN XY: 74140

African (AFR) AF: 0.00130 AC: 54 AN: 41474

American (AMR) AF: 0.00741 AC: 113 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0213 AC: 74 AN: 3470

East Asian (EAS) AF: 0.000967 AC: 5 AN: 5168

South Asian (SAS) AF: 0.00725 AC: 35 AN: 4830

European-Finnish (FIN) AF: 0.00764 AC: 79 AN: 10344

Middle Eastern (MID) AF: 0.0207 AC: 6 AN: 290

European-Non Finnish (NFE) AF: 0.00758 AC: 514 AN: 67814

Other (OTH) AF: 0.00668 AC: 14 AN: 2096

Alfa AF: 0.00598 Hom.: 0

Bravo AF: 0.00547

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.4
DANN	Benign	0.86
PhyloP100		-0.91
PromoterAI		-0.065	Neutral
Mutation Taster		=99/1	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: rs528120489; hg19: chr22-50639570;