2-99155070-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_145199.3(LIPT1):c.-2+19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.609 in 455,270 control chromosomes in the GnomAD database, including 86,043 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.58 (26500 hom., cov: 33)
  • Exomes 𝑓: 0.62 (59543 hom.)
• Consequence: LIPT1 NM_145199.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0210

Genes affected

LIPT1 (HGNC:29569): (lipoyltransferase 1) The process of transferring lipoic acid to proteins is a two-step process. The first step is the activation of lipoic acid by lipoate-activating enzyme to form lipoyl-AMP. For the second step, the protein encoded by this gene transfers the lipoyl moiety to apoproteins. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 13. Read-through transcription also exists between this gene and the neighboring downstream mitochondrial ribosomal protein L30 (MRPL30) gene. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 2-99155070-C-T is Benign according to our data. Variant chr2-99155070-C-T is described in ClinVar as [Benign]. Clinvar id is 379989.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPT1	NM_145199.3	c.-2+19C>T		intron_variant		ENST00000651691.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPT1	ENST00000651691.1	c.-2+19C>T		intron_variant			NM_145199.3	P1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 88247 AN: 152028 Hom.: 26488 Cov.: 33

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.636

Gnomad OTH AF: 0.630

GnomAD3 exomes AF: 0.625 AC: 80740 AN: 129226 Hom.: 25802 AF XY: 0.632 AC XY: 44613 AN XY: 70594

Gnomad AFR exome AF: 0.425

Gnomad AMR exome AF: 0.552

Gnomad ASJ exome AF: 0.633

Gnomad EAS exome AF: 0.872

Gnomad SAS exome AF: 0.626

Gnomad FIN exome AF: 0.578

Gnomad NFE exome AF: 0.637

Gnomad OTH exome AF: 0.620

GnomAD4 exome AF: 0.623 AC: 188845 AN: 303124 Hom.: 59543 Cov.: 0 AF XY: 0.627 AC XY: 108233 AN XY: 172620

Gnomad4 AFR exome AF: 0.435

Gnomad4 AMR exome AF: 0.552

Gnomad4 ASJ exome AF: 0.626

Gnomad4 EAS exome AF: 0.876

Gnomad4 SAS exome AF: 0.624

Gnomad4 FIN exome AF: 0.576

Gnomad4 NFE exome AF: 0.633

Gnomad4 OTH exome AF: 0.622

GnomAD4 genome AF: 0.580 AC: 88291 AN: 152146 Hom.: 26500 Cov.: 33 AF XY: 0.580 AC XY: 43137 AN XY: 74400

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.611

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.878

Gnomad4 SAS AF: 0.623

Gnomad4 FIN AF: 0.558

Gnomad4 NFE AF: 0.637

Gnomad4 OTH AF: 0.633

Alfa AF: 0.609 Hom.: 5209

Bravo AF: 0.576

Asia WGS AF: 0.703 AC: 2445 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 02, 2015

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	8.2
Dann	Benign	0.90

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs2516834; hg19: chr2-99771533;