19-5692033-C-T

Variant names:

• chr19-5692033-C-T
• rs2054832707
• NM_004793.4:c.2879G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_004793.4(LONP1):​c.2879G>A​(p.Ter960Ter) variant causes a stop retained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000405 in 1,233,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: LONP1 NM_004793.4 stop_retained
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.29
• Publications: 0 publications found

Genes affected

LONP1 (HGNC:9479): (lon peptidase 1, mitochondrial) This gene encodes a mitochondrial matrix protein that belongs to the Lon family of ATP-dependent proteases. This protein mediates the selective degradation of misfolded, unassembled or oxidatively damaged polypeptides in the mitochondrial matrix. It may also have a chaperone function in the assembly of inner membrane protein complexes, and participate in the regulation of mitochondrial gene expression and maintenance of the integrity of the mitochondrial genome. Decreased expression of this gene has been noted in a patient with hereditary spastic paraplegia (PMID:18378094). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Feb 2013]

RPL36 (HGNC:13631): (ribosomal protein L36) Ribosomes, the organelles that catalyze protein synthesis, consist of a small 40S subunit and a large 60S subunit. Together these subunits are composed of 4 RNA species and approximately 80 structurally distinct proteins. This gene encodes a ribosomal protein that is a component of the 60S subunit. The protein belongs to the L36E family of ribosomal proteins. It is located in the cytoplasm. Transcript variants derived from alternative splicing exist; they encode the same protein. As is typical for genes encoding ribosomal proteins, there are multiple processed pseudogenes of this gene dispersed through the genome. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP6: Variant 19-5692033-C-T is Benign according to our data. Variant chr19-5692033-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2046473.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.29 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004793.4. 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
	LONP1	NM_004793.4	MANE Select	c.2879G>A	p.Ter960Ter	stop_retained	Exon 18 of 18	NP_004784.2
	LONP1	NM_001276479.2		c.2687G>A	p.Ter896Ter	stop_retained	Exon 19 of 19	NP_001263408.1	P36776-2
	LONP1	NM_001276480.1		c.2291G>A	p.Ter764Ter	stop_retained	Exon 18 of 18	NP_001263409.1	P36776-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LONP1	ENST00000360614.8	TSL:1 MANE Select	c.2879G>A	p.Ter960Ter	stop_retained	Exon 18 of 18	ENSP00000353826.2	P36776-1
	LONP1	ENST00000590729.5	TSL:1	c.2489G>A	p.Ter830Ter	stop_retained	Exon 18 of 18	ENSP00000465139.1	K7EJE8
	LONP1	ENST00000958482.1		c.3065G>A	p.Ter1022Ter	stop_retained	Exon 19 of 19	ENSP00000628541.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000405 AC: 5 AN: 1233156 Hom.: 0 Cov.: 34 AF XY: 0.00000163 AC XY: 1 AN XY: 612910

African (AFR) AF: 0.00 AC: 0 AN: 32048

American (AMR) AF: 0.00 AC: 0 AN: 38276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21428

East Asian (EAS) AF: 0.00 AC: 0 AN: 37342

South Asian (SAS) AF: 0.00 AC: 0 AN: 76038

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42978

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4852

European-Non Finnish (NFE) AF: 0.00000538 AC: 5 AN: 929476

Other (OTH) AF: 0.00 AC: 0 AN: 50718

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	12
DANN	Benign	0.95
PhyloP100		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9

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: rs2054832707; hg19: chr19-5692044; COSMIC: COSV56798952; COSMIC: COSV56798952;