NM_012248.4:c.-302G>A

Variant names:

• chr16-30446029-C-T
• rs4787645
• NM_012248.4:c.-302G>A

Variant summary

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

The NM_012248.4(SEPHS2):​c.-302G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 313,606 control chromosomes in the GnomAD database, including 25,259 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 0.32 (10245 hom., cov: 31)
  • Exomes 𝑓: 0.40 (15014 hom.)
• Consequence: SEPHS2 NM_012248.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240
• Publications: 22 publications found

Genes affected

SEPHS2 (HGNC:19686): (selenophosphate synthetase 2) This gene encodes an enzyme that catalyzes the production of monoselenophosphate (MSP) from selenide and ATP. MSP is the selenium donor required for synthesis of selenocysteine (Sec), which is co-translationally incorporated into selenoproteins at in-frame UGA codons that normally signal translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, the Sec insertion sequence (SECIS) element, which is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. This protein is itself a selenoprotein containing a Sec residue at its active site, suggesting the existence of an autoregulatory mechanism. It is preferentially expressed in tissues implicated in the synthesis of selenoproteins and in sites of blood cell development. A pseudogene for this locus has been identified on chromosome 5. [provided by RefSeq, May 2017]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012248.4. 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
	SEPHS2	NM_012248.4	MANE Select	c.-302G>A		upstream_gene	N/A	NP_036380.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPHS2	ENST00000478753.5	TSL:6 MANE Select	c.-302G>A		upstream_gene	N/A	ENSP00000418669.3	Q99611

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47964 AN: 151652 Hom.: 10235 Cov.: 31

Gnomad AFR AF: 0.0747

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.491

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.343

GnomAD4 exome AF: 0.398 AC: 64488 AN: 161836 Hom.: 15014 Cov.: 2 AF XY: 0.389 AC XY: 32438 AN XY: 83408

African (AFR) AF: 0.0806 AC: 354 AN: 4390

American (AMR) AF: 0.535 AC: 2669 AN: 4988

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 2317 AN: 5866

East Asian (EAS) AF: 0.868 AC: 10192 AN: 11744

South Asian (SAS) AF: 0.170 AC: 1751 AN: 10312

European-Finnish (FIN) AF: 0.494 AC: 6495 AN: 13156

Middle Eastern (MID) AF: 0.352 AC: 287 AN: 816

European-Non Finnish (NFE) AF: 0.364 AC: 36497 AN: 100170

Other (OTH) AF: 0.378 AC: 3926 AN: 10394

GnomAD4 genome AF: 0.316 AC: 47976 AN: 151770 Hom.: 10245 Cov.: 31 AF XY: 0.324 AC XY: 24026 AN XY: 74158

African (AFR) AF: 0.0746 AC: 3091 AN: 41428

American (AMR) AF: 0.480 AC: 7296 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1470 AN: 3472

East Asian (EAS) AF: 0.868 AC: 4459 AN: 5136

South Asian (SAS) AF: 0.172 AC: 828 AN: 4808

European-Finnish (FIN) AF: 0.491 AC: 5161 AN: 10518

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24643 AN: 67908

Other (OTH) AF: 0.343 AC: 720 AN: 2100

Alfa AF: 0.342 Hom.: 14177

Bravo AF: 0.317

Asia WGS AF: 0.453 AC: 1573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	4.7
DANN	Benign	0.71
PhyloP100		-0.024
PromoterAI		-0.17	Neutral
Mutation Taster		=300/0	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: rs4787645; hg19: chr16-30457350; COSMIC: COSV72100740;