19-39515579-C-A

Variant names:

• chr19-39515579-C-A
• rs2079691372
• NM_182704.2:c.367C>A

Variant summary

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

The NM_182704.2(SELENOV):​c.367C>A​(p.Pro123Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,395,680 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P123A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: SELENOV NM_182704.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0540
• Publications: 0 publications found

Genes affected

SELENOV (HGNC:30399): (selenoprotein V) 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, which is necessary for the recognition of UGA as a Sec codon rather than as a stop signal. This protein is specifically expressed in the testis. 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. Alternatively spliced transcript variants have been found for this gene.[provided by RefSeq, Apr 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=0.1434609).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182704.2. 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
	SELENOV	NM_182704.2	MANE Select	c.367C>A	p.Pro123Thr	missense	Exon 1 of 6	NP_874363.1	P59797
	SELENOV	NM_001350809.1		c.367C>A	p.Pro123Thr	missense	Exon 1 of 5	NP_001337738.1
	SELENOV	NR_146916.2		n.157C>A		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SELENOV	ENST00000335426.9	TSL:1 MANE Select	c.367C>A	p.Pro123Thr	missense	Exon 1 of 6	ENSP00000333956.4	P59797
	SELENOV	ENST00000597876.1	TSL:3	n.134C>A		non_coding_transcript_exon	Exon 1 of 2
	SELENOV	ENST00000600586.1	TSL:3	n.-237C>A		upstream_gene	N/A	ENSP00000470671.1	M0QZN9

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1395680 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 688306

African (AFR) AF: 0.00 AC: 0 AN: 31592

American (AMR) AF: 0.00 AC: 0 AN: 35698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25162

East Asian (EAS) AF: 0.00 AC: 0 AN: 35730

South Asian (SAS) AF: 0.00 AC: 0 AN: 78626

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5684

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078714

Other (OTH) AF: 0.0000173 AC: 1 AN: 57946

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.054
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.060
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.14
MutPred		0.26		Gain of phosphorylation at P123 (P = 0.012)
MVP		0.12
MPC		0.62
ClinPred		0.36	T
GERP RS		2.1
PromoterAI		0.036	Neutral
Varity_R		0.16
Mutation Taster		=98/2	polymorphism

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: rs2079691372; hg19: chr19-40006219;