Genetic Variant NM_003009.4:c.29+424C>T (chr19-47779238-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.109

Publications

13 publications found

Variant links:

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]

SELENOW links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELENOW	NM_003009.4 link	c.29+424C>T		intron_variant	Intron 1 of 5	ENST00000601048.6	NP_003000.1	P63302

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELENOW	ENST00000601048.6 link	c.29+424C>T		intron_variant	Intron 1 of 5	1	NM_003009.4	ENSP00000473185.1		P63302

Frequencies

GnomAD3 genomes

AF:

0.622

AC:

94507

AN:

151842

Hom.:

29520

Cov.:

show subpopulations

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.:

AF XY:

0.546

AC XY:

5319

AN XY:

9740

show subpopulations

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:

AN:

108

European-Non Finnish (NFE)

AF:

0.560

AC:

7211

AN:

12872

Other (OTH)

AF:

0.540

AC:

715

AN:

1324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

227

454

681

908

1135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.622

AC:

94595

AN:

151960

Hom.:

29550

Cov.:

AF XY:

0.623

AC XY:

46257

AN XY:

74264

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1806

3612

5418

7224

9030

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

782

1564

2346

3128

3910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.5

(source)

DANN

Benign

0.83

PhyloP100

0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over