NM_001031855.3:c.131A>T

Variant names:

• chrX-118974911-A-T
• rs1459492379
• NM_001031855.3:c.131A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001031855.3(LONRF3):​c.131A>T​(p.Glu44Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000042 in 1,189,989 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 1 hem., cov: 24)
  • Exomes 𝑓: 0.0000028 (0 hom. 0 hem.)
• Consequence: LONRF3 NM_001031855.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.77
• Publications: 1 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3175786).

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.131A>T	p.Glu44Val	missense	Exon 1 of 11	NP_001027026.1	Q496Y0-1
	LONRF3	NM_024778.5		c.131A>T	p.Glu44Val	missense	Exon 1 of 10	NP_079054.3	A8K2D3
	LONRF3	NR_110311.1		n.298A>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.131A>T	p.Glu44Val	missense	Exon 1 of 11	ENSP00000360690.3	Q496Y0-1
	LONRF3	ENST00000304778.11	TSL:1	c.131A>T	p.Glu44Val	missense	Exon 1 of 10	ENSP00000307732.7	Q496Y0-2
	LONRF3	ENST00000961937.1		c.131A>T	p.Glu44Val	missense	Exon 1 of 10	ENSP00000631996.1

Frequencies

GnomAD3 genomes AF: 0.0000177 AC: 2 AN: 113080 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000375

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000145 AC: 2 AN: 137607 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000353

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000279 AC: 3 AN: 1076909 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 348785

African (AFR) AF: 0.00 AC: 0 AN: 26056

American (AMR) AF: 0.00 AC: 0 AN: 32212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18900

East Asian (EAS) AF: 0.00 AC: 0 AN: 29078

South Asian (SAS) AF: 0.00 AC: 0 AN: 51283

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4083

European-Non Finnish (NFE) AF: 0.00000361 AC: 3 AN: 831836

Other (OTH) AF: 0.00 AC: 0 AN: 45227

GnomAD4 genome AF: 0.0000177 AC: 2 AN: 113080 Hom.: 0 Cov.: 24 AF XY: 0.0000284 AC XY: 1 AN XY: 35224

African (AFR) AF: 0.00 AC: 0 AN: 31189

American (AMR) AF: 0.00 AC: 0 AN: 10871

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2657

East Asian (EAS) AF: 0.00 AC: 0 AN: 3562

South Asian (SAS) AF: 0.00 AC: 0 AN: 2772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000375 AC: 2 AN: 53268

Other (OTH) AF: 0.00 AC: 0 AN: 1527

Alfa AF: 0.00 Hom.: 0

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	Benign	0.12
BayesDel_addAF	Benign	-0.017	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.035	T
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.72	T
M_CAP	Pathogenic	0.70	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.8
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.17
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.049	D
Polyphen		0.16	B
Vest4		0.18
MutPred		0.19		Loss of glycosylation at P46 (P = 0.1659)
MVP		0.62
MPC		0.77
ClinPred		0.19	T
GERP RS		0.32
PromoterAI		0.024	Neutral
Varity_R		0.18
gMVP		0.36
Mutation Taster		=97/3	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

dbSNP: rs1459492379; hg19: chrX-118108874;