10-13333906-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_012247.5(SEPHS1):c.471A>G(p.Thr157=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 1,612,738 control chromosomes in the GnomAD database, including 298,423 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.64 (31262 hom., cov: 32)
  • Exomes 𝑓: 0.60 (267161 hom.)
• Consequence: SEPHS1 NM_012247.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.77

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-13333906-T-C is Benign according to our data. Variant chr10-13333906-T-C is described in ClinVar as [Benign]. Clinvar id is 1181340.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.77 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEPHS1	NM_012247.5	c.471A>G	p.Thr157=	synonymous_variant	5/9	ENST00000327347.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEPHS1	ENST00000327347.10	c.471A>G	p.Thr157=	synonymous_variant	5/9	1	NM_012247.5	P1

Frequencies

GnomAD3 genomes AF: 0.639 AC: 97010 AN: 151932 Hom.: 31242 Cov.: 32

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.637

GnomAD3 exomes AF: 0.638 AC: 160300 AN: 251240 Hom.: 51993 AF XY: 0.630 AC XY: 85542 AN XY: 135806

Gnomad AFR exome AF: 0.704

Gnomad AMR exome AF: 0.765

Gnomad ASJ exome AF: 0.586

Gnomad EAS exome AF: 0.797

Gnomad SAS exome AF: 0.623

Gnomad FIN exome AF: 0.597

Gnomad NFE exome AF: 0.583

Gnomad OTH exome AF: 0.603

GnomAD4 exome AF: 0.603 AC: 880336 AN: 1460688 Hom.: 267161 Cov.: 37 AF XY: 0.603 AC XY: 437924 AN XY: 726706

Gnomad4 AFR exome AF: 0.692

Gnomad4 AMR exome AF: 0.762

Gnomad4 ASJ exome AF: 0.583

Gnomad4 EAS exome AF: 0.756

Gnomad4 SAS exome AF: 0.627

Gnomad4 FIN exome AF: 0.596

Gnomad4 NFE exome AF: 0.587

Gnomad4 OTH exome AF: 0.612

GnomAD4 genome AF: 0.638 AC: 97071 AN: 152050 Hom.: 31262 Cov.: 32 AF XY: 0.639 AC XY: 47494 AN XY: 74302

Gnomad4 AFR AF: 0.701

Gnomad4 AMR AF: 0.702

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.772

Gnomad4 SAS AF: 0.626

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.587

Gnomad4 OTH AF: 0.632

Alfa AF: 0.605 Hom.: 12035

Bravo AF: 0.649

Asia WGS AF: 0.664 AC: 2310 AN: 3478

EpiCase AF: 0.585

EpiControl AF: 0.580

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

GeneDx

Apr 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.26
Dann	Benign	0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs10752297; hg19: chr10-13375906; COSMIC: COSV59258344; COSMIC: COSV59258344;