chr16-30445408-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_012248.4(SEPHS2):​c.320G>A​(p.Gly107Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00233 in 1,593,250 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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: 𝑓 0.0018 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0024 (4 hom.)
• Consequence: SEPHS2 NM_012248.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.732
• Publications: 7 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0048159957).
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

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.320G>A	p.Gly107Asp	missense	Exon 1 of 1	NP_036380.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEPHS2	ENST00000478753.5	TSL:6 MANE Select	c.320G>A	p.Gly107Asp	missense	Exon 1 of 1	ENSP00000418669.3	Q99611

Frequencies

GnomAD3 genomes AF: 0.00177 AC: 270 AN: 152246 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000506

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00169

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00268

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00217 AC: 453 AN: 208516 AF XY: 0.00209

Gnomad AFR exome AF: 0.000417

Gnomad AMR exome AF: 0.000877

Gnomad ASJ exome AF: 0.00344

Gnomad EAS exome AF: 0.000191

Gnomad FIN exome AF: 0.00287

Gnomad NFE exome AF: 0.00320

Gnomad OTH exome AF: 0.00169

GnomAD4 exome AF: 0.00239 AC: 3440 AN: 1440886 Hom.: 4 Cov.: 31 AF XY: 0.00235 AC XY: 1686 AN XY: 716000

African (AFR) AF: 0.000603 AC: 20 AN: 33170

American (AMR) AF: 0.000933 AC: 39 AN: 41786

Ashkenazi Jewish (ASJ) AF: 0.00359 AC: 92 AN: 25598

East Asian (EAS) AF: 0.0000256 AC: 1 AN: 39046

South Asian (SAS) AF: 0.00130 AC: 110 AN: 84498

European-Finnish (FIN) AF: 0.00241 AC: 113 AN: 46818

Middle Eastern (MID) AF: 0.000700 AC: 4 AN: 5714

European-Non Finnish (NFE) AF: 0.00267 AC: 2945 AN: 1104608

Other (OTH) AF: 0.00194 AC: 116 AN: 59648

GnomAD4 genome AF: 0.00177 AC: 270 AN: 152364 Hom.: 1 Cov.: 32 AF XY: 0.00154 AC XY: 115 AN XY: 74516

African (AFR) AF: 0.000505 AC: 21 AN: 41594

American (AMR) AF: 0.00183 AC: 28 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4832

European-Finnish (FIN) AF: 0.00169 AC: 18 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00268 AC: 182 AN: 68026

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00170 Hom.: 0

Bravo AF: 0.00197

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00337 AC: 13

ESP6500AA AF: 0.000272 AC: 1

ESP6500EA AF: 0.00294 AC: 24

ExAC AF: 0.00206 AC: 247

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	1.2
DANN	Benign	0.54
DEOGEN2	Benign	0.0062	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0068	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0060	T
MetaRNN	Benign	0.0048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.73
PrimateAI	Benign	0.45	T
PROVEAN	Benign	0.12	N
REVEL	Benign	0.28
Sift	Benign	0.11	T
Sift4G	Benign	0.62	T
Polyphen		0.0010	B
MVP		0.13
ClinPred		0.0028	T
GERP RS		0.79
PromoterAI		-0.16	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.045
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11557070; hg19: chr16-30456729; COSMIC: COSV72100727;