10-13321046-A-T

Variant names:

• chr10-13321046-A-T
• rs10508459
• NM_012247.5:c.965-1690T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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: STRONG, MODERATE Submitted by: G2P, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012247.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPHS1	NM_012247.5	MANE Select	c.965-1690T>A		intron	N/A	NP_036379.2
	SEPHS1	NM_001375769.1		c.959-1690T>A		intron	N/A	NP_001362698.1
	SEPHS1	NM_001195602.2		c.764-1690T>A		intron	N/A	NP_001182531.1	P49903-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPHS1	ENST00000327347.10	TSL:1 MANE Select	c.965-1690T>A		intron	N/A	ENSP00000367893.3	P49903-1
	SEPHS1	ENST00000545675.5	TSL:1	c.764-1690T>A		intron	N/A	ENSP00000441119.2	P49903-3
	SEPHS1	ENST00000378614.8	TSL:1	c.752-1690T>A		intron	N/A	ENSP00000367877.3	P49903-2

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

African (AFR) AF: 0.101 AC: 4205 AN: 41434

American (AMR) AF: 0.518 AC: 7888 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 1238 AN: 3466

East Asian (EAS) AF: 0.655 AC: 3348 AN: 5112

South Asian (SAS) AF: 0.490 AC: 2341 AN: 4782

European-Finnish (FIN) AF: 0.474 AC: 4998 AN: 10554

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.442 AC: 29985 AN: 67848

Other (OTH) AF: 0.406 AC: 854 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.60
PhyloP100		-0.050
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10508459; hg19: chr10-13363046;