10-13321046-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012247.5(SEPHS1):c.965-1690T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,728 control chromosomes in the GnomAD database, including 12,291 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 0.36 (12291 hom., cov: 30)
• Consequence: SEPHS1 NM_012247.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEPHS1	NM_012247.5	c.965-1690T>A		intron_variant		ENST00000327347.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEPHS1	ENST00000327347.10	c.965-1690T>A		intron_variant		1	NM_012247.5	P1
SEPHS1	ENST00000378614.8	c.752-1690T>A		intron_variant		1
SEPHS1	ENST00000545675.5	c.764-1690T>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55223 AN: 151610 Hom.: 12287 Cov.: 30

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.656

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.409

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.364 AC: 55224 AN: 151728 Hom.: 12291 Cov.: 30 AF XY: 0.371 AC XY: 27479 AN XY: 74126

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.655

Gnomad4 SAS AF: 0.490

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.406

Alfa AF: 0.258 Hom.: 723

Bravo AF: 0.358

Asia WGS AF: 0.520 AC: 1808 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.1
Dann	Benign	0.60

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

LitVar

Other links and lift over

dbSNP: rs10508459; hg19: chr10-13363046;