chr19-5691922-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004793.4(LONP1):​c.*110C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0271 in 1,285,064 control chromosomes in the GnomAD database, including 611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 56 hom., cov: 33)
Exomes 𝑓: 0.028 ( 555 hom. )

Consequence

LONP1
NM_004793.4 3_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.795
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 19-5691922-G-A is Benign according to our data. Variant chr19-5691922-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1198795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0222 (3375/152320) while in subpopulation NFE AF= 0.0359 (2440/68038). AF 95% confidence interval is 0.0347. There are 56 homozygotes in gnomad4. There are 1483 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 56 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LONP1NM_004793.4 linkuse as main transcriptc.*110C>T 3_prime_UTR_variant 18/18 ENST00000360614.8
RPL36NM_033643.3 linkuse as main transcript downstream_gene_variant ENST00000347512.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LONP1ENST00000360614.8 linkuse as main transcriptc.*110C>T 3_prime_UTR_variant 18/181 NM_004793.4 P1P36776-1
RPL36ENST00000347512.8 linkuse as main transcript downstream_gene_variant 1 NM_033643.3 P1

Frequencies

GnomAD3 genomes
AF:
0.0222
AC:
3377
AN:
152202
Hom.:
56
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00628
Gnomad AMI
AF:
0.155
Gnomad AMR
AF:
0.0226
Gnomad ASJ
AF:
0.0173
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00456
Gnomad FIN
AF:
0.00330
Gnomad MID
AF:
0.0222
Gnomad NFE
AF:
0.0359
Gnomad OTH
AF:
0.0315
GnomAD4 exome
AF:
0.0278
AC:
31450
AN:
1132744
Hom.:
555
Cov.:
16
AF XY:
0.0271
AC XY:
15276
AN XY:
562774
show subpopulations
Gnomad4 AFR exome
AF:
0.00463
Gnomad4 AMR exome
AF:
0.0177
Gnomad4 ASJ exome
AF:
0.0177
Gnomad4 EAS exome
AF:
0.0000818
Gnomad4 SAS exome
AF:
0.00720
Gnomad4 FIN exome
AF:
0.00508
Gnomad4 NFE exome
AF:
0.0329
Gnomad4 OTH exome
AF:
0.0258
GnomAD4 genome
AF:
0.0222
AC:
3375
AN:
152320
Hom.:
56
Cov.:
33
AF XY:
0.0199
AC XY:
1483
AN XY:
74476
show subpopulations
Gnomad4 AFR
AF:
0.00628
Gnomad4 AMR
AF:
0.0225
Gnomad4 ASJ
AF:
0.0173
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00435
Gnomad4 FIN
AF:
0.00330
Gnomad4 NFE
AF:
0.0359
Gnomad4 OTH
AF:
0.0312
Alfa
AF:
0.0227
Hom.:
16
Bravo
AF:
0.0246
Asia WGS
AF:
0.00577
AC:
20
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Likely benign, criteria provided, single submitterclinical testingGeneDxSep 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
3.3
DANN
Benign
0.74

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs11551019; hg19: chr19-5691933; API