Genetic Variant NM_012247.5:c.751+36G>A (chr10-13328315-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_012247.5(SEPHS1):c.751+36G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 1,380,884 control chromosomes in the GnomAD database, including 190,224 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 0.45 ( 17097 hom., cov: 31)

Exomes 𝑓: 0.52 ( 173127 hom. )

Consequence

SEPHS1
NM_012247.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.733

Publications

9 publications found

Variant links:

Genes affected

SEPHS1 (HGNC:19685): (selenophosphate synthetase 1) This gene encodes an enzyme that synthesizes selenophosphate from selenide and ATP. Selenophosphate is the selenium donor used to synthesize selenocysteine, which is co-translationally incorporated into selenoproteins at in-frame UGA codons. [provided by RefSeq, Sep 2010]

SEPHS1 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AD Classification: MODERATE Submitted by: G2P

SEPHS1 links:

Genome browser will be placed here

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=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPHS1	NM_012247.5 link	c.751+36G>A		intron_variant	Intron 7 of 8	ENST00000327347.10	NP_036379.2	P49903-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SEPHS1	ENST00000327347.10 link	c.751+36G>A	intron_variant	Intron 7 of 8	1	NM_012247.5	ENSP00000367893.3	P49903-1
SEPHS1	ENST00000545675.5 link	c.550+36G>A	intron_variant	Intron 6 of 7	1		ENSP00000441119.2	P49903-3
SEPHS1	ENST00000378614.8 link	c.751+36G>A	intron_variant	Intron 7 of 7	1		ENSP00000367877.3	P49903-2

Frequencies

GnomAD3 genomes

AF:

0.447

AC:

67826

AN:

151758

Hom.:

17099

Cov.:

show subpopulations

Gnomad AFR

AF:

0.206

Gnomad AMI

AF:

0.404

Gnomad AMR

AF:

0.599

Gnomad ASJ

AF:

0.455

Gnomad EAS

AF:

0.774

Gnomad SAS

AF:

0.598

Gnomad FIN

AF:

0.523

Gnomad MID

AF:

0.433

Gnomad NFE

AF:

0.511

Gnomad OTH

AF:

0.488

GnomAD2 exomes

AF:

0.544

AC:

132352

AN:

243390

AF XY:

0.545

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.703

Gnomad ASJ exome

AF:

0.460

Gnomad EAS exome

AF:

0.797

Gnomad FIN exome

AF:

0.517

Gnomad NFE exome

AF:

0.508

Gnomad OTH exome

AF:

0.519

GnomAD4 exome

AF:

0.524

AC:

643554

AN:

1229008

Hom.:

173127

Cov.:

AF XY:

0.526

AC XY:

327720

AN XY:

622984

show subpopulations

African (AFR)

AF:

0.189

AC:

5409

AN:

28594

American (AMR)

AF:

0.695

AC:

29129

AN:

41940

Ashkenazi Jewish (ASJ)

AF:

0.460

AC:

11183

AN:

24336

East Asian (EAS)

AF:

0.756

AC:

29141

AN:

38560

South Asian (SAS)

AF:

0.596

AC:

47611

AN:

79926

European-Finnish (FIN)

AF:

0.520

AC:

27683

AN:

53234

Middle Eastern (MID)

AF:

0.458

AC:

2041

AN:

4460

European-Non Finnish (NFE)

AF:

0.513

AC:

464007

AN:

905134

Other (OTH)

AF:

0.518

AC:

27350

AN:

52824

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

14851

29703

44554

59406

74257

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12336

24672

37008

49344

61680

<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:

0.447

AC:

67840

AN:

151876

Hom.:

17097

Cov.:

AF XY:

0.453

AC XY:

33614

AN XY:

74212

show subpopulations

African (AFR)

AF:

0.206

AC:

8520

AN:

41442

American (AMR)

AF:

0.600

AC:

9142

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.455

AC:

1579

AN:

3470

East Asian (EAS)

AF:

0.773

AC:

3985

AN:

5154

South Asian (SAS)

AF:

0.596

AC:

2853

AN:

4784

European-Finnish (FIN)

AF:

0.523

AC:

5522

AN:

10562

Middle Eastern (MID)

AF:

0.425

AC:

124

AN:

292

European-Non Finnish (NFE)

AF:

0.511

AC:

34731

AN:

67920

Other (OTH)

AF:

0.484

AC:

1016

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1724

3447

5171

6894

8618

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

624

1248

1872

2496

3120

<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:

0.459

Hom.:

3607

Bravo

AF:

0.443

Asia WGS

AF:

0.619

AC:

2155

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.4

(source)

DANN

Benign

0.52

PhyloP100

-0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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