chr8-12731758-C-T

Variant names:

• chr8-12731758-C-T
• NM_152271.5:c.1666G>A

Variant summary

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

The NM_152271.5(LONRF1):​c.1666G>A​(p.Glu556Lys) variant causes a missense change involving the alteration of a 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: 32)
• Consequence: LONRF1 NM_152271.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57
• Publications: 0 publications found

Genes affected

LONRF1 (HGNC:26302): (LON peptidase N-terminal domain and ring finger 1) Predicted to enable metal ion binding activity. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

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_152271.5. 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
	LONRF1	NM_152271.5	MANE Select	c.1666G>A	p.Glu556Lys	missense	Exon 8 of 12	NP_689484.3
	LONRF1	NM_001329976.2		c.1633G>A	p.Glu545Lys	missense	Exon 8 of 12	NP_001316905.1	Q17RB8-2
	LONRF1	NR_138255.2		n.1673-2426G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LONRF1	ENST00000398246.8	TSL:5 MANE Select	c.1666G>A	p.Glu556Lys	missense	Exon 8 of 12	ENSP00000381298.3	Q17RB8-1
	LONRF1	ENST00000526680.5	TSL:1	n.*504G>A		non_coding_transcript_exon	Exon 8 of 12	ENSP00000434090.1	E9PRX6
	LONRF1	ENST00000526680.5	TSL:1	n.*504G>A		3_prime_UTR	Exon 8 of 12	ENSP00000434090.1	E9PRX6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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	0.28
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.093	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Uncertain	0.10	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Uncertain	0.48	D
MutationAssessor	Uncertain	2.7	M
PhyloP100		7.6
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.59
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.013	D
Polyphen		0.61	P
Vest4		0.29
MutPred		0.38		Gain of ubiquitination at E556 (P = 0.0138)
MVP		0.69
MPC		1.7
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.62
gMVP		0.77
Mutation Taster		=45/55	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr8-12589267;