10-13319976-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPHS1	NM_012247.5	c.965-620T>C		intron_variant	Intron 8 of 8	ENST00000327347.10	NP_036379.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEPHS1	ENST00000327347.10	c.965-620T>C		intron_variant	Intron 8 of 8	1	NM_012247.5	ENSP00000367893.3
SEPHS1	ENST00000545675.5	c.764-620T>C		intron_variant	Intron 7 of 7	1		ENSP00000441119.2
SEPHS1	ENST00000378614.8	c.752-620T>C		intron_variant	Intron 7 of 7	1		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

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.474

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.409

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.446

Alfa AF: 0.464 Hom.: 2180

Bravo AF: 0.461

Asia WGS AF: 0.356 AC: 1236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.5
DANN	Benign	0.46

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: rs1747683; hg19: chr10-13361976;