11-57742822-A-G

Variant names:

• chr11-57742822-A-G
• rs9420
• NM_170746.4:c.*31-41A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_170746.4(SELENOH):​c.*31-41A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 152,680 control chromosomes in the GnomAD database, including 36,133 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.69 (35991 hom., cov: 30)
  • Exomes 𝑓: 0.57 (142 hom.)
• Consequence: SELENOH NM_170746.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900
• Publications: 58 publications found

Genes affected

SELENOH (HGNC:18251): (selenoprotein H) This gene encodes a nucleolar protein, which belongs to the SelWTH family. It functions as an oxidoreductase, and has been shown to protect neurons against UVB-induced damage by inhibiting apoptotic cell death pathways, promote mitochondrial biogenesis and mitochondrial function, and suppress cellular senescence through genome maintenance and redox regulation. This protein is a selenoprotein, containing the rare amino acid selenocysteine (Sec) 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, May 2016]

ENSG00000254732 (HGNC:):

TMX2 (HGNC:30739): (thioredoxin related transmembrane protein 2) This gene encodes a member of the disulfide isomerase (PDI) family of endoplasmic reticulum (ER) proteins that catalyze protein folding and thiol-disulfide interchange reactions. The encoded protein has an N-terminal ER-signal sequence, a catalytically active thioredoxin domain, one transmembrane domain and a C-terminal ER-retention sequence. This protein is enriched on the mitochondria-associated-membrane of the ER via palmitoylation of two of its cytosolically exposed cysteines. [provided by RefSeq, Jan 2017]

TMX2-CTNND1 (HGNC:41992): (TMX2-CTNND1 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring TMX2 (thioredoxin-related transmembrane protein 2) and CTNND1 (catenin, cadherin-associated protein, delta 1) genes on chromosome 11. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is therefore unlikely to produce a protein product. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170746.4. 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
	SELENOH	NM_170746.4	MANE Select	c.*31-41A>G		intron	N/A	NP_734467.1	Q8IZQ5
	SELENOH	NM_001321335.2		c.*11-41A>G		intron	N/A	NP_001308264.1	Q8IZQ5
	TMX2-CTNND1	NR_037646.1		n.346+5154A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOH	ENST00000534355.6	TSL:1 MANE Select	c.*31-41A>G		intron	N/A	ENSP00000434511.1	Q8IZQ5
	SELENOH	ENST00000533321.1	TSL:1	n.1219A>G		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000254732	ENST00000531074.1	TSL:3	n.*31-41A>G		intron	N/A	ENSP00000457993.1	H3BV83

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104112 AN: 151756 Hom.: 35975 Cov.: 30

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.775

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.889

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.704

GnomAD4 exome AF: 0.573 AC: 462 AN: 806 Hom.: 142 Cov.: 0 AF XY: 0.552 AC XY: 253 AN XY: 458

African (AFR) AF: 0.500 AC: 7 AN: 14

American (AMR) AF: 0.833 AC: 20 AN: 24

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 6 AN: 10

East Asian (EAS) AF: 0.833 AC: 20 AN: 24

South Asian (SAS) AF: 0.500 AC: 6 AN: 12

European-Finnish (FIN) AF: 0.567 AC: 261 AN: 460

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.534 AC: 124 AN: 232

Other (OTH) AF: 0.571 AC: 16 AN: 28

GnomAD4 genome AF: 0.686 AC: 104167 AN: 151874 Hom.: 35991 Cov.: 30 AF XY: 0.687 AC XY: 51024 AN XY: 74222

African (AFR) AF: 0.655 AC: 27121 AN: 41382

American (AMR) AF: 0.776 AC: 11825 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 2421 AN: 3468

East Asian (EAS) AF: 0.888 AC: 4591 AN: 5168

South Asian (SAS) AF: 0.719 AC: 3459 AN: 4814

European-Finnish (FIN) AF: 0.630 AC: 6639 AN: 10542

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45824 AN: 67952

Other (OTH) AF: 0.706 AC: 1482 AN: 2100

Alfa AF: 0.690 Hom.: 115397

Bravo AF: 0.701

Asia WGS AF: 0.790 AC: 2750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.8
DANN	Benign	0.73
PhyloP100		-0.090
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: rs9420; hg19: chr11-57510294;