rs768753376

Variant names:

• chrX-118975175-C-A
• rs768753376
• NM_001031855.3:c.395C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-118975175-C-A
• chrX-118975175-C-G

Variant summary

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

The NM_001031855.3(LONRF3):​c.395C>A​(p.Ala132Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000941 in 1,062,727 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A132G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.4e-7 (0 hom. 0 hem.)
• Consequence: LONRF3 NM_001031855.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0200

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.083513886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LONRF3	NM_001031855.3	c.395C>A	p.Ala132Glu	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.395C>A	p.Ala132Glu	missense_variant	Exon 1 of 11	1	NM_001031855.3	ENSP00000360690.3
LONRF3	ENST00000304778.11	c.395C>A	p.Ala132Glu	missense_variant	Exon 1 of 10	1		ENSP00000307732.7
LONRF3	ENST00000481285.5	n.395C>A		non_coding_transcript_exon_variant	Exon 1 of 11	2		ENSP00000435426.1
LONRF3	ENST00000439603.5	c.-188C>A		upstream_gene_variant		1		ENSP00000414519.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 9.41e-7 AC: 1 AN: 1062727 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 346357

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000357

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	7.5
DANN	Benign	0.75
DEOGEN2	Benign	0.0074	.;T
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.34	T;T
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.084	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.81	L;L
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.44	N;N
REVEL	Benign	0.19
Sift	Benign	0.41	T;T
Sift4G	Benign	0.73	T;T
Polyphen		0.0010	B;B
Vest4		0.075
MutPred		0.24		Gain of relative solvent accessibility (P = 0.1012);Gain of relative solvent accessibility (P = 0.1012);
MVP		0.60
MPC		0.47
ClinPred		0.036	T
GERP RS		0.12
Varity_R		0.098
gMVP		0.40

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: rs768753376; hg19: chrX-118109138;