chr16-30445408-C-A

Variant names:

• chr16-30445408-C-A
• rs11557070
• NM_012248.4:c.320G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012248.4(SEPHS2):​c.320G>T​(p.Gly107Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000486 in 1,440,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G107A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: SEPHS2 NM_012248.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.732

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06653553).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEPHS2	NM_012248.4	c.320G>T	p.Gly107Val	missense_variant	Exon 1 of 1	ENST00000478753.5	NP_036380.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEPHS2	ENST00000478753.5	c.320G>T	p.Gly107Val	missense_variant	Exon 1 of 1	6	NM_012248.4	ENSP00000418669.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000480 AC: 1 AN: 208516 Hom.: 0 AF XY: 0.00000869 AC XY: 1 AN XY: 115032

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000635

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000486 AC: 7 AN: 1440890 Hom.: 0 Cov.: 31 AF XY: 0.00000838 AC XY: 6 AN XY: 716004

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000634

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	1.4
DANN	Benign	0.50
DEOGEN2	Benign	0.0066	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.088
Sift	Benign	0.20	T
Sift4G	Benign	0.48	T
Polyphen		0.046	B
MutPred		0.39		Loss of disorder (P = 0.0413);
MVP		0.18
ClinPred		0.25	T
GERP RS		0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.032

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: rs11557070; hg19: chr16-30456729;