8-12728959-T-C

Variant names:

• chr8-12728959-T-C
• NM_152271.5:c.1952A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152271.5(LONRF1):​c.1952A>G​(p.Lys651Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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: 0.0950

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05170673).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LONRF1	NM_152271.5	c.1952A>G	p.Lys651Arg	missense_variant	Exon 10 of 12	ENST00000398246.8	NP_689484.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LONRF1	ENST00000398246.8	c.1952A>G	p.Lys651Arg	missense_variant	Exon 10 of 12	5	NM_152271.5	ENSP00000381298.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 23, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1952A>G (p.K651R) alteration is located in exon 10 (coding exon 10) of the LONRF1 gene. This alteration results from a A to G substitution at nucleotide position 1952, causing the lysine (K) at amino acid position 651 to be replaced by an arginine (R). 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	0.068
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	16
DANN	Benign	0.96
DEOGEN2	Benign	0.0036	T;.;T;T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.84	T;.;D;D
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.052	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.97	N;.;.;.
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.42	N;N;N;N
REVEL	Benign	0.036
Sift	Benign	0.69	T;T;T;T
Sift4G	Benign	0.90	T;T;T;T
Polyphen		0.0010	B;.;.;.
Vest4		0.14
MutPred		0.44		Gain of loop (P = 0.0312);.;.;.;
MVP		0.14
MPC		0.53
ClinPred		0.56	D
GERP RS		2.6
Varity_R		0.023
gMVP		0.34

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: chr8-12586468;