chr19-5691976-T-TCAGTTCTGGCCCAGACAGGGCCTGACATC

Position:

• chr19-5691976-T-TCAGTTCTGGCCCAGACAGGGCCTGACATC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004793.4(LONP1):​c.*55_*56insGATGTCAGGCCCTGTCTGGGCCAGAACTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,531,706 control chromosomes in the GnomAD database, including 67,672 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4914 hom., cov: 32)
  • Exomes 𝑓: 0.29 (62758 hom.)
• Consequence: LONP1 NM_004793.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0240

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 19-5691976-T-TCAGTTCTGGCCCAGACAGGGCCTGACATC is Benign according to our data. Variant chr19-5691976-T-TCAGTTCTGGCCCAGACAGGGCCTGACATC is described in ClinVar as [Benign]. Clinvar id is 1258867.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LONP1	NM_004793.4	c.*55_*56insGATGTCAGGCCCTGTCTGGGCCAGAACTG		3_prime_UTR_variant	18/18	ENST00000360614.8	NP_004784.2
LONP1	NM_001276479.2	c.*55_*56insGATGTCAGGCCCTGTCTGGGCCAGAACTG		3_prime_UTR_variant	19/19		NP_001263408.1
LONP1	NM_001276480.1	c.*55_*56insGATGTCAGGCCCTGTCTGGGCCAGAACTG		3_prime_UTR_variant	18/18		NP_001263409.1
LONP1	NR_076392.2	n.2740_2741insGATGTCAGGCCCTGTCTGGGCCAGAACTG		non_coding_transcript_exon_variant	19/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LONP1	ENST00000360614.8	c.*55_*56insGATGTCAGGCCCTGTCTGGGCCAGAACTG		3_prime_UTR_variant	18/18	1	NM_004793.4	ENSP00000353826	P1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35037 AN: 151470 Hom.: 4919 Cov.: 32

Gnomad AFR AF: 0.0800

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.0928

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.236

GnomAD4 exome AF: 0.292 AC: 402757 AN: 1380118 Hom.: 62758 Cov.: 34 AF XY: 0.290 AC XY: 197068 AN XY: 680336

Gnomad4 AFR exome AF: 0.0659

Gnomad4 AMR exome AF: 0.190

Gnomad4 ASJ exome AF: 0.236

Gnomad4 EAS exome AF: 0.0840

Gnomad4 SAS exome AF: 0.196

Gnomad4 FIN exome AF: 0.307

Gnomad4 NFE exome AF: 0.318

Gnomad4 OTH exome AF: 0.276

GnomAD4 genome AF: 0.231 AC: 35031 AN: 151588 Hom.: 4914 Cov.: 32 AF XY: 0.230 AC XY: 17064 AN XY: 74052

Gnomad4 AFR AF: 0.0798

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.0928

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.321

Gnomad4 OTH AF: 0.233

Alfa AF: 0.193 Hom.: 654

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 03, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3835296; hg19: chr19-5691987;