5-115963268-G-C

Position:

• chr5-115963268-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173800.5(LVRN):​c.651G>C​(p.Arg217Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LVRN NM_173800.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0930

Genes affected

LVRN (HGNC:26904): (laeverin) Predicted to enable metalloaminopeptidase activity; peptide binding activity; and zinc ion binding activity. Predicted to be involved in several processes, including peptide catabolic process; proteolysis; and regulation of blood pressure. Predicted to be integral component of membrane. Predicted to be active in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=0.0785113).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LVRN	NM_173800.5	c.651G>C	p.Arg217Ser	missense_variant	1/20	ENST00000357872.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LVRN	ENST00000357872.9	c.651G>C	p.Arg217Ser	missense_variant	1/20	1	NM_173800.5	P1
LVRN	ENST00000504467.5	c.651G>C	p.Arg217Ser	missense_variant, NMD_transcript_variant	1/20	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 78

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 17, 2023

The c.651G>C (p.R217S) alteration is located in exon 1 (coding exon 1) of the LVRN gene. This alteration results from a G to C substitution at nucleotide position 651, causing the arginine (R) at amino acid position 217 to be replaced by a serine (S). 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
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	9.0
DANN	Benign	0.96
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.49	T;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.079	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.79	D;N
PrimateAI	Benign	0.31	T
Sift4G	Benign	0.77	T;T
Polyphen		0.0010	.;B
Vest4		0.12
MutPred		0.57		.;Loss of solvent accessibility (P = 0.0299);
MVP		0.20
MPC		0.085
ClinPred		0.045	T
GERP RS		1.8
Varity_R		0.077
gMVP		0.52

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: chr5-115298965;