chr10-13328315-C-T

Variant names:

• chr10-13328315-C-T
• rs3740211
• NM_012247.5:c.751+36G>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.751+36G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 1,380,884 control chromosomes in the GnomAD database, including 190,224 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 0.45 (17097 hom., cov: 31)
  • Exomes 𝑓: 0.52 (173127 hom.)
• Consequence: SEPHS1 NM_012247.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.733
• 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: 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.753 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.751+36G>A		intron	N/A	NP_036379.2
	SEPHS1	NM_001375769.1		c.751+36G>A		intron	N/A	NP_001362698.1
	SEPHS1	NM_001195602.2		c.550+36G>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.751+36G>A		intron	N/A	ENSP00000367893.3	P49903-1
	SEPHS1	ENST00000545675.5	TSL:1	c.550+36G>A		intron	N/A	ENSP00000441119.2	P49903-3
	SEPHS1	ENST00000378614.8	TSL:1	c.751+36G>A		intron	N/A	ENSP00000367877.3	P49903-2

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67826 AN: 151758 Hom.: 17099 Cov.: 31

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.488

GnomAD2 exomes AF: 0.544 AC: 132352 AN: 243390 AF XY: 0.545

Gnomad AFR exome AF: 0.201

Gnomad AMR exome AF: 0.703

Gnomad ASJ exome AF: 0.460

Gnomad EAS exome AF: 0.797

Gnomad FIN exome AF: 0.517

Gnomad NFE exome AF: 0.508

Gnomad OTH exome AF: 0.519

GnomAD4 exome AF: 0.524 AC: 643554 AN: 1229008 Hom.: 173127 Cov.: 16 AF XY: 0.526 AC XY: 327720 AN XY: 622984

African (AFR) AF: 0.189 AC: 5409 AN: 28594

American (AMR) AF: 0.695 AC: 29129 AN: 41940

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 11183 AN: 24336

East Asian (EAS) AF: 0.756 AC: 29141 AN: 38560

South Asian (SAS) AF: 0.596 AC: 47611 AN: 79926

European-Finnish (FIN) AF: 0.520 AC: 27683 AN: 53234

Middle Eastern (MID) AF: 0.458 AC: 2041 AN: 4460

European-Non Finnish (NFE) AF: 0.513 AC: 464007 AN: 905134

Other (OTH) AF: 0.518 AC: 27350 AN: 52824

GnomAD4 genome AF: 0.447 AC: 67840 AN: 151876 Hom.: 17097 Cov.: 31 AF XY: 0.453 AC XY: 33614 AN XY: 74212

African (AFR) AF: 0.206 AC: 8520 AN: 41442

American (AMR) AF: 0.600 AC: 9142 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1579 AN: 3470

East Asian (EAS) AF: 0.773 AC: 3985 AN: 5154

South Asian (SAS) AF: 0.596 AC: 2853 AN: 4784

European-Finnish (FIN) AF: 0.523 AC: 5522 AN: 10562

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.511 AC: 34731 AN: 67920

Other (OTH) AF: 0.484 AC: 1016 AN: 2100

Alfa AF: 0.459 Hom.: 3607

Bravo AF: 0.443

Asia WGS AF: 0.619 AC: 2155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.52
PhyloP100		-0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3740211; hg19: chr10-13370315;