2-99158360-A-C

Position:

• chr2-99158360-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_145199.3(LIPT1):​c.-2+3309A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 150,878 control chromosomes in the GnomAD database, including 1,755 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.13 (1755 hom., cov: 28)
• Consequence: LIPT1 NM_145199.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.335

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 2-99158360-A-C is Benign according to our data. Variant chr2-99158360-A-C is described in ClinVar as [Benign]. Clinvar id is 1278684.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPT1	NM_145199.3	c.-2+3309A>C		intron_variant		ENST00000651691.1	NP_660200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPT1	ENST00000651691.1	c.-2+3309A>C		intron_variant			NM_145199.3	ENSP00000498546	P1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19647 AN: 150782 Hom.: 1755 Cov.: 28

Gnomad AFR AF: 0.0328

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0916

Gnomad EAS AF: 0.0123

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.135

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.130 AC: 19644 AN: 150878 Hom.: 1755 Cov.: 28 AF XY: 0.129 AC XY: 9497 AN XY: 73600

Gnomad4 AFR AF: 0.0327

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0916

Gnomad4 EAS AF: 0.0123

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.139

Alfa AF: 0.152 Hom.: 254

Bravo AF: 0.119

Asia WGS AF: 0.0830 AC: 289 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	3.2
DANN	Benign	0.56

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: rs112377545; hg19: chr2-99774823;