11-57742822-A-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_170746.4(SELENOH):​c.*31-41A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

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>T		intron	N/A	NP_734467.1	Q8IZQ5
	SELENOH	NM_001321335.2		c.*11-41A>T		intron	N/A	NP_001308264.1	Q8IZQ5
	TMX2-CTNND1	NR_037646.1		n.346+5154A>T		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>T		intron	N/A	ENSP00000434511.1	Q8IZQ5
	SELENOH	ENST00000533321.1	TSL:1	n.1219A>T		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000254732	ENST00000531074.1	TSL:3	n.*31-41A>T		intron	N/A	ENSP00000457993.1	H3BV83

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151828 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 806 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 458

African (AFR) AF: 0.00 AC: 0 AN: 14

American (AMR) AF: 0.00 AC: 0 AN: 24

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10

East Asian (EAS) AF: 0.00 AC: 0 AN: 24

South Asian (SAS) AF: 0.00 AC: 0 AN: 12

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 460

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 232

Other (OTH) AF: 0.00 AC: 0 AN: 28

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151828 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74140

African (AFR) AF: 0.00 AC: 0 AN: 41290

American (AMR) AF: 0.00 AC: 0 AN: 15232

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10546

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67978

Other (OTH) AF: 0.00 AC: 0 AN: 2084

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.4
DANN	Benign	0.75
PhyloP100		-0.090
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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;