19-39515579-C-G

Variant names:

• chr19-39515579-C-G
• rs2079691372
• NM_182704.2:c.367C>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>G​(p.Pro123Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,395,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: SELENOV NM_182704.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.13336927).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SELENOV	NM_182704.2	c.367C>G	p.Pro123Ala	missense_variant	Exon 1 of 6	ENST00000335426.9	NP_874363.1
SELENOV	NM_001350809.1	c.367C>G	p.Pro123Ala	missense_variant	Exon 1 of 5		NP_001337738.1
SELENOV	NR_146916.2	n.157C>G		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>G	p.Pro123Ala	missense_variant	Exon 1 of 6	1	NM_182704.2	ENSP00000333956.4
SELENOV	ENST00000597876.1	n.134C>G		non_coding_transcript_exon_variant	Exon 1 of 2	3
SELENOV	ENST00000600586.1	n.-237C>G		upstream_gene_variant		3		ENSP00000470671.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000129 AC: 18 AN: 1395680 Hom.: 0 Cov.: 32 AF XY: 0.0000131 AC XY: 9 AN XY: 688306

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000397

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000158

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 21, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.367C>G (p.P123A) alteration is located in exon 1 (coding exon 1) of the SELV gene. This alteration results from a C to G substitution at nucleotide position 367, causing the proline (P) at amino acid position 123 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.056	T;.;.
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.49	T;T;T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.13	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.4	N;D;.
REVEL	Benign	0.034
Sift	Pathogenic	0.0	D;D;.
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.96	D;.;.
Vest4		0.13
MVP		0.13
MPC		0.50
ClinPred		0.33	T
GERP RS		2.1
Varity_R		0.11

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: rs2079691372; hg19: chr19-40006219;