10-13344754-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_012247.5(SEPHS1):c.193+4G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000491 in 1,491,682 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00096 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00044 (4 hom.)
• Consequence: SEPHS1 NM_012247.5 splice_donor_region, intron
• Scores: Splicing: ADA: 0.0009729
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00500

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 10-13344754-C-T is Benign according to our data. Variant chr10-13344754-C-T is described in ClinVar as [Benign]. Clinvar id is 788597.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEPHS1	NM_012247.5	c.193+4G>A		splice_donor_region_variant, intron_variant		ENST00000327347.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEPHS1	ENST00000327347.10	c.193+4G>A		splice_donor_region_variant, intron_variant		1	NM_012247.5	P1

Frequencies

GnomAD3 genomes AF: 0.000973 AC: 148 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00384

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00198 AC: 395 AN: 199242 Hom.: 3 AF XY: 0.00150 AC XY: 162 AN XY: 108112

Gnomad AFR exome AF: 0.000517

Gnomad AMR exome AF: 0.0139

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00324

Gnomad SAS exome AF: 0.000192

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000316

Gnomad OTH exome AF: 0.00111

GnomAD4 exome AF: 0.000438 AC: 587 AN: 1339398 Hom.: 4 Cov.: 30 AF XY: 0.000360 AC XY: 236 AN XY: 655656

Gnomad4 AFR exome AF: 0.000436

Gnomad4 AMR exome AF: 0.0126

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00234

Gnomad4 SAS exome AF: 0.000154

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000211

Gnomad4 OTH exome AF: 0.000675

GnomAD4 genome AF: 0.000959 AC: 146 AN: 152284 Hom.: 0 Cov.: 32 AF XY: 0.00103 AC XY: 77 AN XY: 74464

Gnomad4 AFR AF: 0.000457

Gnomad4 AMR AF: 0.00647

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00366

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000478 Hom.: 0

Bravo AF: 0.00168

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	6.7
Dann	Benign	0.88

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00097
dbscSNV1_RF	Benign	0.20
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

LitVar

Other links and lift over

dbSNP: rs117211901; hg19: chr10-13386754;