chr19-47779238-C-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003009.4(SELENOW):​c.29+424C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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>G		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>G		intron	N/A	ENSP00000473185.1	P63302
	SELENOW	ENST00000595615.1	TSL:1	c.29+424C>G		intron	N/A	ENSP00000470941.1	P63302
	SELENOW	ENST00000593892.5	TSL:3	c.29+424C>G		intron	N/A	ENSP00000471149.1	P63302

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 19316 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 9830

African (AFR) AF: 0.00 AC: 0 AN: 728

American (AMR) AF: 0.00 AC: 0 AN: 482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 814

East Asian (EAS) AF: 0.00 AC: 0 AN: 1180

South Asian (SAS) AF: 0.00 AC: 0 AN: 830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 108

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 12986

Other (OTH) AF: 0.00 AC: 0 AN: 1334

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 47815

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.69
PhyloP100		0.11

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;