19-47779238-C-T

Position:

• chr19-47779238-C-T

Variant summary

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

The NM_003009.4(SELENOW):​c.29+424C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 171,090 control chromosomes in the GnomAD database, including 32,439 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 0.62 (29550 hom., cov: 32)
  • Exomes 𝑓: 0.54 (2889 hom.)
• Consequence: SELENOW NM_003009.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.109

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SELENOW	NM_003009.4	c.29+424C>T		intron_variant		ENST00000601048.6	NP_003000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SELENOW	ENST00000601048.6	c.29+424C>T		intron_variant		1	NM_003009.4	ENSP00000473185	P1

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94507 AN: 151842 Hom.: 29520 Cov.: 32

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.605

GnomAD4 exome AF: 0.543 AC: 10380 AN: 19130 Hom.: 2889 Cov.: 0 AF XY: 0.546 AC XY: 5319 AN XY: 9740

Gnomad4 AFR exome AF: 0.492

Gnomad4 AMR exome AF: 0.525

Gnomad4 ASJ exome AF: 0.434

Gnomad4 EAS exome AF: 0.472

Gnomad4 SAS exome AF: 0.586

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.560

Gnomad4 OTH exome AF: 0.540

GnomAD4 genome AF: 0.622 AC: 94595 AN: 151960 Hom.: 29550 Cov.: 32 AF XY: 0.623 AC XY: 46257 AN XY: 74264

Gnomad4 AFR AF: 0.584

Gnomad4 AMR AF: 0.647

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.546

Gnomad4 SAS AF: 0.667

Gnomad4 FIN AF: 0.601

Gnomad4 NFE AF: 0.651

Gnomad4 OTH AF: 0.606

Alfa AF: 0.621 Hom.: 5555

Bravo AF: 0.617

Asia WGS AF: 0.606 AC: 2109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.83

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: rs10412896; hg19: chr19-48282495;