2-99156412-T-C

Variant summary

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

The ENST00000393473.6(LIPT1):c.-16T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 152,018 control chromosomes in the GnomAD database, including 29,778 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.62 (29750 hom., cov: 30)
  • Exomes 𝑓: 0.70 (28 hom.)
• Consequence: LIPT1 ENST00000393473.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.55

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=-1.05).
• BP6: Variant 2-99156412-T-C is Benign according to our data. Variant chr2-99156412-T-C is described in ClinVar as [Benign]. Clinvar id is 379990.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPT1	NM_145199.3	c.-2+1361T>C		intron_variant		ENST00000651691.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPT1	ENST00000651691.1	c.-2+1361T>C		intron_variant			NM_145199.3	P1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94264 AN: 151790 Hom.: 29712 Cov.: 30

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.727

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.884

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.774

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.661

GnomAD4 exome AF: 0.700 AC: 77 AN: 110 Hom.: 28 Cov.: 0 AF XY: 0.675 AC XY: 54 AN XY: 80

Gnomad4 AFR exome AF: 0.833

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.875

Gnomad4 NFE exome AF: 0.686

Gnomad4 OTH exome AF: 0.750

GnomAD4 genome AF: 0.621 AC: 94349 AN: 151908 Hom.: 29750 Cov.: 30 AF XY: 0.619 AC XY: 45983 AN XY: 74238

Gnomad4 AFR AF: 0.538

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.650

Gnomad4 EAS AF: 0.884

Gnomad4 SAS AF: 0.629

Gnomad4 FIN AF: 0.567

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.665

Alfa AF: 0.622 Hom.: 3508

Bravo AF: 0.621

Asia WGS AF: 0.721 AC: 2510 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 04, 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	-1.1
Cadd	Benign	0.48
Dann	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2516828; hg19: chr2-99772875;