X-118974844-G-C

Position:

• chrX-118974844-G-C

Variant summary

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

The NM_001031855.3(LONRF3):​c.64G>C​(p.Glu22Gln) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 24)
• Consequence: LONRF3 NM_001031855.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.40

Genes affected

LONRF3 (HGNC:21152): (LON peptidase N-terminal domain and ring finger 3) The protein encoded by this gene contains a RING finger domain, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. Multiple alternatively spliced transcript variants have been suggested, but their full length natures are not clear. [provided by RefSeq, Jul 2008]

LONRF3 (HGNC:):

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=0.14407972).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LONRF3	NM_001031855.3	c.64G>C	p.Glu22Gln	missense_variant	1/11	ENST00000371628.8	NP_001027026.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LONRF3	ENST00000371628.8	c.64G>C	p.Glu22Gln	missense_variant	1/11	1	NM_001031855.3	ENSP00000360690.3
LONRF3	ENST00000304778.11	c.64G>C	p.Glu22Gln	missense_variant	1/10	1		ENSP00000307732.7
LONRF3	ENST00000481285.5	n.64G>C		non_coding_transcript_exon_variant	1/11	2		ENSP00000435426.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 24

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

Oct 01, 2024

The c.64G>C (p.E22Q) alteration is located in exon 1 (coding exon 1) of the LONRF3 gene. This alteration results from a G to C substitution at nucleotide position 64, causing the glutamic acid (E) at amino acid position 22 to be replaced by a glutamine (Q). 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	0.090
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	.;T
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.60	T;T
M_CAP	Pathogenic	0.48	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.59	N;N
REVEL	Benign	0.14
Sift	Uncertain	0.015	D;D
Sift4G	Uncertain	0.029	D;D
Polyphen		0.23	B;B
Vest4		0.15
MutPred		0.16		Gain of relative solvent accessibility (P = 0.0289);Gain of relative solvent accessibility (P = 0.0289);
MVP		0.50
MPC		0.50
ClinPred		0.38	T
GERP RS		2.9
Varity_R		0.16
gMVP		0.32

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: chrX-118108807;