2-99155127-G-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+76G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 446,016 control chromosomes in the GnomAD database, including 84,745 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.58 (26506 hom., cov: 33)
  • Exomes 𝑓: 0.63 (58239 hom.)
• Consequence: LIPT1 NM_145199.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.531

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 2-99155127-G-T is Benign according to our data. Variant chr2-99155127-G-T is described in ClinVar as [Benign]. Clinvar id is 1294394.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+76G>T		intron_variant		ENST00000651691.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPT1	ENST00000651691.1	c.-2+76G>T		intron_variant			NM_145199.3	P1

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88246 AN: 151974 Hom.: 26494 Cov.: 33

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.630

GnomAD4 exome AF: 0.626 AC: 183936 AN: 293924 Hom.: 58239 Cov.: 0 AF XY: 0.630 AC XY: 105344 AN XY: 167160

Gnomad4 AFR exome AF: 0.437

Gnomad4 AMR exome AF: 0.557

Gnomad4 ASJ exome AF: 0.629

Gnomad4 EAS exome AF: 0.876

Gnomad4 SAS exome AF: 0.625

Gnomad4 FIN exome AF: 0.576

Gnomad4 NFE exome AF: 0.636

Gnomad4 OTH exome AF: 0.627

GnomAD4 genome AF: 0.581 AC: 88290 AN: 152092 Hom.: 26506 Cov.: 33 AF XY: 0.580 AC XY: 43134 AN XY: 74346

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.611

Gnomad4 ASJ AF: 0.619

Gnomad4 EAS AF: 0.878

Gnomad4 SAS AF: 0.623

Gnomad4 FIN AF: 0.559

Gnomad4 NFE AF: 0.637

Gnomad4 OTH AF: 0.633

Alfa AF: 0.596 Hom.: 3405

Bravo AF: 0.576

Asia WGS AF: 0.703 AC: 2446 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	-0.87
Cadd	Benign	5.2
Dann	Benign	0.89

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: rs2632260; hg19: chr2-99771590; COSMIC: COSV56782464; COSMIC: COSV56782464;