rs528032711

Variant names:

• chr19-47780732-T-G
• rs528032711
• NM_003009.4:c.37T>G

Your query was ambiguous. Multiple possible variants found:

• chr19-47780732-T-G
• chr19-47780732-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM4 BS2

The NM_003009.4(SELENOW):​c.37T>G​(p.Ter13Glyext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000614 in 1,563,138 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000066 (2 hom.)
• Consequence: SELENOW NM_003009.4 stop_lost
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.18
• Publications: 0 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.

• PM4: Stoplost variant in NM_003009.4 Downstream stopcodon found after 39 codons.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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.37T>G	p.Ter13Glyext*?	stop_lost	Exon 2 of 6	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.37T>G	p.Ter13Glyext*?	stop_lost	Exon 2 of 6	ENSP00000473185.1	P63302
	SELENOW	ENST00000595615.1	TSL:1	c.37T>G	p.Ter13Glyext*?	stop_lost	Exon 2 of 5	ENSP00000470941.1	P63302
	SELENOW	ENST00000593892.5	TSL:3	c.37T>G	p.Ter13Glyext*?	stop_lost	Exon 2 of 6	ENSP00000471149.1	P63302

Frequencies

GnomAD3 genomes AF: 0.0000199 AC: 3 AN: 150930 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000211

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000169 AC: 30 AN: 177238 AF XY: 0.000255

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000275

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000659 AC: 93 AN: 1412090 Hom.: 2 Cov.: 30 AF XY: 0.000106 AC XY: 74 AN XY: 697686

African (AFR) AF: 0.00 AC: 0 AN: 32324

American (AMR) AF: 0.00 AC: 0 AN: 36968

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25410

East Asian (EAS) AF: 0.00 AC: 0 AN: 37120

South Asian (SAS) AF: 0.00102 AC: 82 AN: 80314

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5714

European-Non Finnish (NFE) AF: 0.00000737 AC: 8 AN: 1085516

Other (OTH) AF: 0.0000512 AC: 3 AN: 58562

GnomAD4 genome AF: 0.0000199 AC: 3 AN: 151048 Hom.: 0 Cov.: 28 AF XY: 0.0000407 AC XY: 3 AN XY: 73664

African (AFR) AF: 0.00 AC: 0 AN: 41268

American (AMR) AF: 0.00 AC: 0 AN: 14962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5036

South Asian (SAS) AF: 0.000211 AC: 1 AN: 4736

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10474

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67808

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000197 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.000169 AC: 20

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	22
DANN	Uncertain	0.97
Eigen	Benign	0.069
Eigen_PC	Benign	0.089
FATHMM_MKL	Benign	0.75	D
PhyloP100		1.2
GERP RS		3.2
Mutation Taster		=73/127	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs528032711; hg19: chr19-48283989;