X-118975306-A-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LONRF3	NM_001031855.3	c.526A>T	p.Thr176Ser	missense_variant	Exon 1 of 11	ENST00000371628.8	NP_001027026.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LONRF3	ENST00000371628.8	c.526A>T	p.Thr176Ser	missense_variant	Exon 1 of 11	1	NM_001031855.3	ENSP00000360690.3
LONRF3	ENST00000304778.11	c.526A>T	p.Thr176Ser	missense_variant	Exon 1 of 10	1		ENSP00000307732.7
LONRF3	ENST00000481285.5	n.526A>T		non_coding_transcript_exon_variant	Exon 1 of 11	2		ENSP00000435426.1
LONRF3	ENST00000439603.5	c.-57A>T		upstream_gene_variant		1		ENSP00000414519.1

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

Dec 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.526A>T (p.T176S) alteration is located in exon 1 (coding exon 1) of the LONRF3 gene. This alteration results from a A to T substitution at nucleotide position 526, causing the threonine (T) at amino acid position 176 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	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;T
M_CAP	Pathogenic	0.98	D
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	0.53	N;N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.7	N;N
REVEL	Uncertain	0.52
Sift	Benign	0.34	T;T
Sift4G	Benign	0.45	T;T
Polyphen		0.95	P;P
Vest4		0.33
MutPred		0.64		Gain of disorder (P = 0.0567);Gain of disorder (P = 0.0567);
MVP		0.75
MPC		1.1
ClinPred		0.43	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.39

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-118109269;