11-57742822-A-G

Position:

• chr11-57742822-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

TMX2-CTNND1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELENOH	NM_170746.4	c.*31-41A>G		intron_variant		ENST00000534355.6
TMX2-CTNND1	NR_037646.1	n.346+5154A>G		intron_variant, non_coding_transcript_variant
SELENOH	NM_001321335.2	c.*11-41A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELENOH	ENST00000534355.6	c.*31-41A>G		intron_variant		1	NM_170746.4	P1
SELENOH	ENST00000533321.1	n.1219A>G		non_coding_transcript_exon_variant	2/2	1
SELENOH	ENST00000528798.1	c.*11-41A>G		intron_variant		2
SELENOH	ENST00000534386.2	n.388-41A>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.833

Gnomad4 ASJ exome AF: 0.600

Gnomad4 EAS exome AF: 0.833

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.567

Gnomad4 NFE exome AF: 0.534

Gnomad4 OTH exome AF: 0.571

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

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.776

Gnomad4 ASJ AF: 0.698

Gnomad4 EAS AF: 0.888

Gnomad4 SAS AF: 0.719

Gnomad4 FIN AF: 0.630

Gnomad4 NFE AF: 0.674

Gnomad4 OTH AF: 0.706

Alfa AF: 0.683 Hom.: 46432

Bravo AF: 0.701

Asia WGS AF: 0.790 AC: 2750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.8
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs9420; hg19: chr11-57510294;