2-99158468-C-A

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+3417C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.054 in 147,580 control chromosomes in the GnomAD database, including 422 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.054 (422 hom., cov: 31)
• Consequence: LIPT1 NM_145199.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.246

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=-0.91).
• BP6: Variant 2-99158468-C-A is Benign according to our data. Variant chr2-99158468-C-A is described in ClinVar as [Benign]. Clinvar id is 1251402.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPT1	NM_145199.3	c.-2+3417C>A		intron_variant		ENST00000651691.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPT1	ENST00000651691.1	c.-2+3417C>A		intron_variant			NM_145199.3	P1

Frequencies

GnomAD3 genomes AF: 0.0539 AC: 7959 AN: 147544 Hom.: 424 Cov.: 31

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0869

Gnomad ASJ AF: 0.0229

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.0327

Gnomad FIN AF: 0.0244

Gnomad MID AF: 0.0230

Gnomad NFE AF: 0.0152

Gnomad OTH AF: 0.0547

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0540 AC: 7965 AN: 147580 Hom.: 422 Cov.: 31 AF XY: 0.0553 AC XY: 3961 AN XY: 71626

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.0868

Gnomad4 ASJ AF: 0.0229

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.0324

Gnomad4 FIN AF: 0.0244

Gnomad4 NFE AF: 0.0151

Gnomad4 OTH AF: 0.0548

Alfa AF: 0.0324 Hom.: 27

Bravo AF: 0.0626

Asia WGS AF: 0.0980 AC: 338 AN: 3478

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

Jun 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.2
Dann	Benign	0.68

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

Other links and lift over

dbSNP: rs78003746; hg19: chr2-99774931;