10-13319976-A-G

Variant names:

• chr10-13319976-A-G
• rs1747683
• NM_012247.5:c.965-620T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012247.5(SEPHS1):​c.965-620T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 152,022 control chromosomes in the GnomAD database, including 17,043 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 0.46 (17043 hom., cov: 32)
• Consequence: SEPHS1 NM_012247.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.924
• Publications: 9 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: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.609 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPHS1	NM_012247.5	MANE Select	c.965-620T>C		intron	N/A	NP_036379.2
	SEPHS1	NM_001375769.1		c.959-620T>C		intron	N/A	NP_001362698.1
	SEPHS1	NM_001195602.2		c.764-620T>C		intron	N/A	NP_001182531.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPHS1	ENST00000327347.10	TSL:1 MANE Select	c.965-620T>C		intron	N/A	ENSP00000367893.3
	SEPHS1	ENST00000545675.5	TSL:1	c.764-620T>C		intron	N/A	ENSP00000441119.2
	SEPHS1	ENST00000378614.8	TSL:1	c.752-620T>C		intron	N/A	ENSP00000367877.3

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69975 AN: 151902 Hom.: 17008 Cov.: 32

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.229

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.461 AC: 70070 AN: 152022 Hom.: 17043 Cov.: 32 AF XY: 0.456 AC XY: 33889 AN XY: 74286

African (AFR) AF: 0.615 AC: 25508 AN: 41464

American (AMR) AF: 0.340 AC: 5190 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1644 AN: 3470

East Asian (EAS) AF: 0.230 AC: 1188 AN: 5170

South Asian (SAS) AF: 0.384 AC: 1850 AN: 4812

European-Finnish (FIN) AF: 0.409 AC: 4311 AN: 10550

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.425 AC: 28887 AN: 67960

Other (OTH) AF: 0.446 AC: 943 AN: 2112

Alfa AF: 0.497 Hom.: 7319

Bravo AF: 0.461

Asia WGS AF: 0.356 AC: 1236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.5
DANN	Benign	0.46
PhyloP100		0.92
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: rs1747683; hg19: chr10-13361976;