NM_003009.4:c.94G>C

Variant names:

• chr19-47780903-G-C
• rs373200586
• NM_003009.4:c.94G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003009.4(SELENOW):​c.94G>C​(p.Gly32Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,461,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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. G32S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: SELENOW NM_003009.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45
• Publications: 0 publications found

Genes affected

SELENOW (HGNC:10752): (selenoprotein W) This gene encodes a selenoprotein containing a selenocysteine (Sec) residue, which is encoded by the UGA codon that normally signals translation termination. The 3' UTRs of selenoprotein mRNAs contain a conserved stem-loop structure, the Sec insertion sequence (SECIS) element that is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. This protein is highly expressed in skeletal muscle, heart and brain. It belongs to the SelWTH family, which possesses a thioredoxin-like fold and a conserved CxxU (C is cysteine, U is Sec) motif, suggesting a redox function for this gene. Studies in mouse show that this selenoprotein is involved in muscle growth and differentiation, and in the protection of neurons from oxidative stress during neuronal development. A retroprocessed pseudogene of this locus has been identified on chromosome 1. [provided by RefSeq, Aug 2017]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25632098).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003009.4. 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
	SELENOW	NM_003009.4	MANE Select	c.94G>C	p.Gly32Arg	missense	Exon 3 of 6	NP_003000.1	P63302

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOW	ENST00000601048.6	TSL:1 MANE Select	c.94G>C	p.Gly32Arg	missense	Exon 3 of 6	ENSP00000473185.1	P63302
	SELENOW	ENST00000595615.1	TSL:1	c.94G>C	p.Gly32Arg	missense	Exon 3 of 5	ENSP00000470941.1	P63302
	SELENOW	ENST00000593892.5	TSL:3	c.94G>C	p.Gly32Arg	missense	Exon 3 of 6	ENSP00000471149.1	P63302

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 247914 AF XY: 0.0000149

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS 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: 0.00000890 AC: 13 AN: 1461304 Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9 AN XY: 726902

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111676

Other (OTH) AF: 0.00 AC: 0 AN: 60354

GnomAD4 genome Cov.: 30

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.067	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.5
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.044
Sift	Benign	0.099	T
Sift4G	Benign	0.18	T
Polyphen		0.76	P
Vest4		0.52
MutPred		0.29		Gain of solvent accessibility (P = 0.0037)
MVP		0.52
MPC		0.13
ClinPred		0.38	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.040
Mutation Taster		=94/6	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: rs373200586; hg19: chr19-48284160;