rs3786777

chr19-47782906-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003009.4(SELENOW):c.*19-1384A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 152,180 control chromosomes in the GnomAD database, including 13,894 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 0.38 (13878 hom., cov: 32)
  • Exomes 𝑓: 0.50 (16 hom.)
• Consequence: SELENOW NM_003009.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0470

Genes affected

SELENOW (HGNC:10752): (selenoprotein W) This gene encodes a selenoprotein containing a selenocysteine (Sec) residue, which is encoded by the UGA codon that normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, the Sec insertion sequence (SECIS) element that is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. This protein is highly expressed in skeletal muscle, heart and brain. It belongs to the SelWTH family, which possesses a thioredoxin-like fold and a conserved CxxU (C is cysteine, U is Sec) motif, suggesting a redox function for this gene. Studies in mouse show that this selenoprotein is involved in muscle growth and differentiation, and in the protection of neurons from oxidative stress during neuronal development. A retroprocessed pseudogene of this locus has been identified on chromosome 1. [provided by RefSeq, Aug 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SELENOW	NM_003009.4	c.*19-1384A>C		intron_variant		ENST00000601048.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SELENOW	ENST00000601048.6	c.*19-1384A>C		intron_variant		1	NM_003009.4	P1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58564 AN: 151978 Hom.: 13886 Cov.: 32

Gnomad AFR AF: 0.0977

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.509

Gnomad OTH AF: 0.372

GnomAD4 exome AF: 0.500 AC: 42 AN: 84 Hom.: 16 Cov.: 0 AF XY: 0.516 AC XY: 32 AN XY: 62

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.534

Gnomad4 OTH exome AF: 0.625

GnomAD4 genome AF: 0.385 AC: 58555 AN: 152096 Hom.: 13878 Cov.: 32 AF XY: 0.391 AC XY: 29074 AN XY: 74318

Gnomad4 AFR AF: 0.0974

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.581

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.509

Gnomad4 OTH AF: 0.372

Alfa AF: 0.489 Hom.: 37241

Bravo AF: 0.361

Asia WGS AF: 0.479 AC: 1668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.92
Dann	Benign	0.40

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: rs3786777; hg19: chr19-48286163;