10-13333906-T-A

Variant names:

• chr10-13333906-T-A
• rs10752297
• NM_012247.5:c.471A>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_012247.5(SEPHS1):​c.471A>T​(p.Thr157Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T157T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SEPHS1 NM_012247.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.77
• Publications: 23 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP7: Synonymous conserved (PhyloP=-2.77 with no splicing effect.

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.471A>T	p.Thr157Thr	synonymous	Exon 5 of 9	NP_036379.2
	SEPHS1	NM_001375769.1		c.471A>T	p.Thr157Thr	synonymous	Exon 5 of 9	NP_001362698.1
	SEPHS1	NM_001195602.2		c.270A>T	p.Thr90Thr	synonymous	Exon 4 of 8	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.471A>T	p.Thr157Thr	synonymous	Exon 5 of 9	ENSP00000367893.3	P49903-1
	SEPHS1	ENST00000545675.5	TSL:1	c.270A>T	p.Thr90Thr	synonymous	Exon 4 of 8	ENSP00000441119.2	P49903-3
	SEPHS1	ENST00000378614.8	TSL:1	c.471A>T	p.Thr157Thr	synonymous	Exon 5 of 8	ENSP00000367877.3	P49903-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.15
DANN	Benign	0.49
PhyloP100		-2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs10752297; hg19: chr10-13375906;