8-12729056-C-T

Position:

• chr8-12729056-C-T

Variant summary

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

The NM_152271.5(LONRF1):​c.1855G>A​(p.Asp619Asn) 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: 33)
• Consequence: LONRF1 NM_152271.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91

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]

LONRF1 (HGNC:):

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/exons	MANE	Protein	UniProt
LONRF1	NM_152271.5	c.1855G>A	p.Asp619Asn	missense_variant	10/12	ENST00000398246.8	NP_689484.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LONRF1	ENST00000398246.8	c.1855G>A	p.Asp619Asn	missense_variant	10/12	5	NM_152271.5	ENSP00000381298.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 11, 2023

The c.1855G>A (p.D619N) alteration is located in exon 10 (coding exon 10) of the LONRF1 gene. This alteration results from a G to A substitution at nucleotide position 1855, causing the aspartic acid (D) at amino acid position 619 to be replaced by an asparagine (N). 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	Benign	0.19
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.085	T;.;T;T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;.;D;D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.73	D;D;D;D
MetaSVM	Benign	-0.37	T
MutationAssessor	Uncertain	2.6	M;.;.;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.79	T
PROVEAN	Uncertain	-3.8	D;D;D;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0030	D;D;D;D
Sift4G	Uncertain	0.0050	D;T;D;D
Polyphen		1.0	D;.;.;.
Vest4		0.95
MutPred		0.58		Loss of phosphorylation at Y620 (P = 0.0947);.;.;.;
MVP		0.63
MPC		1.6
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.67
gMVP		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: chr8-12586565;