chr8-12738013-A-T

Position:

• chr8-12738013-A-T

Variant summary

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

The NM_152271.5(LONRF1):​c.1095T>A​(p.Asn365Lys) 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: 0.260

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 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=0.06196323).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LONRF1	NM_152271.5	c.1095T>A	p.Asn365Lys	missense_variant	4/12	ENST00000398246.8	NP_689484.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LONRF1	ENST00000398246.8	c.1095T>A	p.Asn365Lys	missense_variant	4/12	5	NM_152271.5	ENSP00000381298.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

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

Jun 22, 2023

The c.1095T>A (p.N365K) alteration is located in exon 4 (coding exon 4) of the LONRF1 gene. This alteration results from a T to A substitution at nucleotide position 1095, causing the asparagine (N) at amino acid position 365 to be replaced by a lysine (K). 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	0.089
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.89
DANN	Benign	0.62
DEOGEN2	Benign	0.0050	T;T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.81
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.22	T;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.062	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	0.34	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.010	N;N
REVEL	Benign	0.049
Sift	Benign	0.90	T;T
Sift4G	Benign	0.92	T;T
Polyphen		0.0010	B;.
Vest4		0.074
MutPred		0.24		Gain of ubiquitination at N365 (P = 0.0025);.;
MVP		0.50
MPC		0.0022
ClinPred		0.030	T
GERP RS		2.7
Varity_R		0.038
gMVP		0.12

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-12595522; COSMIC: COSV101238281; COSMIC: COSV101238281;