rs11551019

Variant names:

• chr19-5691922-G-A
• rs11551019
• NM_004793.4:c.*110C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-5691922-G-A
• chr19-5691922-G-C
• chr19-5691922-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.795
• Publications: 5 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: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 56 AR,AD,XL gene

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.*110C>T		3_prime_UTR	Exon 18 of 18	NP_004784.2
	LONP1	NM_001276479.2		c.*110C>T		3_prime_UTR	Exon 19 of 19	NP_001263408.1	P36776-2
	LONP1	NM_001276480.1		c.*110C>T		3_prime_UTR	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.*110C>T		3_prime_UTR	Exon 18 of 18	ENSP00000353826.2	P36776-1
	LONP1	ENST00000958482.1		c.*110C>T		3_prime_UTR	Exon 19 of 19	ENSP00000628541.1
	LONP1	ENST00000877980.1		c.*110C>T		3_prime_UTR	Exon 19 of 19	ENSP00000548039.1

Frequencies

GnomAD3 genomes AF: 0.0222 AC: 3377 AN: 152202 Hom.: 56 Cov.: 33

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

African (AFR) AF: 0.00463 AC: 124 AN: 26786

American (AMR) AF: 0.0177 AC: 479 AN: 27012

Ashkenazi Jewish (ASJ) AF: 0.0177 AC: 329 AN: 18602

East Asian (EAS) AF: 0.0000818 AC: 3 AN: 36682

South Asian (SAS) AF: 0.00720 AC: 468 AN: 64996

European-Finnish (FIN) AF: 0.00508 AC: 208 AN: 40938

Middle Eastern (MID) AF: 0.0289 AC: 106 AN: 3664

European-Non Finnish (NFE) AF: 0.0329 AC: 28482 AN: 865512

Other (OTH) AF: 0.0258 AC: 1251 AN: 48552

GnomAD4 genome AF: 0.0222 AC: 3375 AN: 152320 Hom.: 56 Cov.: 33 AF XY: 0.0199 AC XY: 1483 AN XY: 74476

African (AFR) AF: 0.00628 AC: 261 AN: 41552

American (AMR) AF: 0.0225 AC: 345 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00435 AC: 21 AN: 4824

European-Finnish (FIN) AF: 0.00330 AC: 35 AN: 10620

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0359 AC: 2440 AN: 68038

Other (OTH) AF: 0.0312 AC: 66 AN: 2114

Alfa AF: 0.0267 Hom.: 138

Bravo AF: 0.0246

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.3
DANN	Benign	0.74
PhyloP100		-0.80
Mutation Taster		=100/0	polymorphism

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: rs11551019; hg19: chr19-5691933;