19-47779238-C-T

Variant names:

• chr19-47779238-C-T
• rs10412896
• NM_003009.4:c.29+424C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003009.4. 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
	SELENOW	NM_003009.4	MANE Select	c.29+424C>T		intron	N/A	NP_003000.1	P63302

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOW	ENST00000601048.6	TSL:1 MANE Select	c.29+424C>T		intron	N/A	ENSP00000473185.1	P63302
	SELENOW	ENST00000595615.1	TSL:1	c.29+424C>T		intron	N/A	ENSP00000470941.1	P63302
	SELENOW	ENST00000593892.5	TSL:3	c.29+424C>T		intron	N/A	ENSP00000471149.1	P63302

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

African (AFR) AF: 0.492 AC: 357 AN: 726

American (AMR) AF: 0.525 AC: 250 AN: 476

Ashkenazi Jewish (ASJ) AF: 0.434 AC: 351 AN: 808

East Asian (EAS) AF: 0.472 AC: 547 AN: 1160

South Asian (SAS) AF: 0.586 AC: 482 AN: 822

European-Finnish (FIN) AF: 0.500 AC: 417 AN: 834

Middle Eastern (MID) AF: 0.463 AC: 50 AN: 108

European-Non Finnish (NFE) AF: 0.560 AC: 7211 AN: 12872

Other (OTH) AF: 0.540 AC: 715 AN: 1324

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

African (AFR) AF: 0.584 AC: 24210 AN: 41438

American (AMR) AF: 0.647 AC: 9879 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1911 AN: 3470

East Asian (EAS) AF: 0.546 AC: 2802 AN: 5132

South Asian (SAS) AF: 0.667 AC: 3214 AN: 4822

European-Finnish (FIN) AF: 0.601 AC: 6354 AN: 10576

Middle Eastern (MID) AF: 0.531 AC: 155 AN: 292

European-Non Finnish (NFE) AF: 0.651 AC: 44263 AN: 67952

Other (OTH) AF: 0.606 AC: 1279 AN: 2110

Alfa AF: 0.640 Hom.: 47815

Bravo AF: 0.617

Asia WGS AF: 0.606 AC: 2109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.83
PhyloP100		0.11
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: rs10412896; hg19: chr19-48282495;