rs2079691372

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-39515579-C-A
• chr19-39515579-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/18 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. 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1434609).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELENOV	NM_182704.2	c.367C>A	p.Pro123Thr	missense_variant	Exon 1 of 6	ENST00000335426.9	NP_874363.1
SELENOV	NM_001350809.1	c.367C>A	p.Pro123Thr	missense_variant	Exon 1 of 5		NP_001337738.1
SELENOV	NR_146916.2	n.157C>A		non_coding_transcript_exon_variant	Exon 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SELENOV	ENST00000335426.9	c.367C>A	p.Pro123Thr	missense_variant	Exon 1 of 6	1	NM_182704.2	ENSP00000333956.4
SELENOV	ENST00000597876.1	n.134C>A		non_coding_transcript_exon_variant	Exon 1 of 2	3
SELENOV	ENST00000600586.1	n.-237C>A		upstream_gene_variant		3		ENSP00000470671.1

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

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: 0.00

Gnomad4 OTH exome AF: 0.0000173

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.14	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.81	L;.;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.1	N;N;.
REVEL	Benign	0.060
Sift	Pathogenic	0.0	D;D;.
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.99	D;.;.
Vest4		0.14
MutPred		0.26		Gain of phosphorylation at P123 (P = 0.012);Gain of phosphorylation at P123 (P = 0.012);Gain of phosphorylation at P123 (P = 0.012);
MVP		0.12
MPC		0.62
ClinPred		0.36	T
GERP RS		2.1
Varity_R		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-40006219;