chrX-118975306-A-T

Variant names:

• chrX-118975306-A-T
• NM_001031855.3:c.526A>T

Variant summary

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

The NM_001031855.3(LONRF3):​c.526A>T​(p.Thr176Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 24)
• Consequence: LONRF3 NM_001031855.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.18
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031855.3. 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
	LONRF3	NM_001031855.3	MANE Select	c.526A>T	p.Thr176Ser	missense	Exon 1 of 11	NP_001027026.1	Q496Y0-1
	LONRF3	NM_024778.5		c.526A>T	p.Thr176Ser	missense	Exon 1 of 10	NP_079054.3	A8K2D3
	LONRF3	NR_110311.1		n.693A>T		non_coding_transcript_exon	Exon 1 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LONRF3	ENST00000371628.8	TSL:1 MANE Select	c.526A>T	p.Thr176Ser	missense	Exon 1 of 11	ENSP00000360690.3	Q496Y0-1
	LONRF3	ENST00000304778.11	TSL:1	c.526A>T	p.Thr176Ser	missense	Exon 1 of 10	ENSP00000307732.7	Q496Y0-2
	LONRF3	ENST00000961937.1		c.526A>T	p.Thr176Ser	missense	Exon 1 of 10	ENSP00000631996.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 24

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	22
DANN	Benign	0.95
DEOGEN2	Benign	0.019	T
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.70	T
M_CAP	Pathogenic	0.98	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	0.53	N
PhyloP100		2.2
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.52
Sift	Benign	0.34	T
Sift4G	Benign	0.45	T
Polyphen		0.95	P
Vest4		0.33
MutPred		0.64		Gain of disorder (P = 0.0567)
MVP		0.75
MPC		1.1
ClinPred		0.43	T
GERP RS		3.2
PromoterAI		0.17	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.39
Mutation Taster		=92/8	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

hg19: chrX-118109269;