NM_012247.5:c.471A>G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_012247.5(SEPHS1):​c.471A>G​(p.Thr157Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 1,612,738 control chromosomes in the GnomAD database, including 298,423 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (31262 hom., cov: 32)
  • Exomes 𝑓: 0.60 (267161 hom.)
• Consequence: SEPHS1 NM_012247.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 10-13333906-T-C is Benign according to our data. Variant chr10-13333906-T-C is described in ClinVar as Benign. ClinVar VariationId is 1181340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.77 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.752 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.471A>G	p.Thr157Thr	synonymous	Exon 5 of 9	NP_036379.2
	SEPHS1	NM_001375769.1		c.471A>G	p.Thr157Thr	synonymous	Exon 5 of 9	NP_001362698.1
	SEPHS1	NM_001195602.2		c.270A>G	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>G	p.Thr157Thr	synonymous	Exon 5 of 9	ENSP00000367893.3	P49903-1
	SEPHS1	ENST00000545675.5	TSL:1	c.270A>G	p.Thr90Thr	synonymous	Exon 4 of 8	ENSP00000441119.2	P49903-3
	SEPHS1	ENST00000378614.8	TSL:1	c.471A>G	p.Thr157Thr	synonymous	Exon 5 of 8	ENSP00000367877.3	P49903-2

Frequencies

GnomAD3 genomes AF: 0.639 AC: 97010 AN: 151932 Hom.: 31242 Cov.: 32

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.637

GnomAD2 exomes AF: 0.638 AC: 160300 AN: 251240 AF XY: 0.630

Gnomad AFR exome AF: 0.704

Gnomad AMR exome AF: 0.765

Gnomad ASJ exome AF: 0.586

Gnomad EAS exome AF: 0.797

Gnomad FIN exome AF: 0.597

Gnomad NFE exome AF: 0.583

Gnomad OTH exome AF: 0.603

GnomAD4 exome AF: 0.603 AC: 880336 AN: 1460688 Hom.: 267161 Cov.: 37 AF XY: 0.603 AC XY: 437924 AN XY: 726706

African (AFR) AF: 0.692 AC: 23130 AN: 33434

American (AMR) AF: 0.762 AC: 34062 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 15230 AN: 26126

East Asian (EAS) AF: 0.756 AC: 30024 AN: 39690

South Asian (SAS) AF: 0.627 AC: 54083 AN: 86190

European-Finnish (FIN) AF: 0.596 AC: 31818 AN: 53414

Middle Eastern (MID) AF: 0.580 AC: 3341 AN: 5762

European-Non Finnish (NFE) AF: 0.587 AC: 651740 AN: 1111052

Other (OTH) AF: 0.612 AC: 36908 AN: 60336

GnomAD4 genome AF: 0.638 AC: 97071 AN: 152050 Hom.: 31262 Cov.: 32 AF XY: 0.639 AC XY: 47494 AN XY: 74302

African (AFR) AF: 0.701 AC: 29078 AN: 41470

American (AMR) AF: 0.702 AC: 10730 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1983 AN: 3470

East Asian (EAS) AF: 0.772 AC: 3972 AN: 5142

South Asian (SAS) AF: 0.626 AC: 3018 AN: 4820

European-Finnish (FIN) AF: 0.606 AC: 6398 AN: 10564

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.587 AC: 39890 AN: 67990

Other (OTH) AF: 0.632 AC: 1335 AN: 2112

Alfa AF: 0.606 Hom.: 12214

Bravo AF: 0.649

Asia WGS AF: 0.664 AC: 2310 AN: 3478

EpiCase AF: 0.585

EpiControl AF: 0.580

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.26
DANN	Benign	0.40
PhyloP100		-2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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; COSMIC: COSV59258344; COSMIC: COSV59258344;