2-99156738-T-G

Position:

• chr2-99156738-T-G

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+1687T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 152,134 control chromosomes in the GnomAD database, including 29,800 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (29799 hom., cov: 33)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: LIPT1 NM_145199.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.604

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=-0.96).
• BP6: Variant 2-99156738-T-G is Benign according to our data. Variant chr2-99156738-T-G is described in ClinVar as [Benign]. Clinvar id is 1258591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
LIPT1	NM_145199.3	c.-2+1687T>G		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+1687T>G		intron_variant			NM_145199.3	ENSP00000498546	P1

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94413 AN: 152014 Hom.: 29761 Cov.: 33

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.884

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.661

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 FIN exome AF: 1.00

GnomAD4 genome AF: 0.621 AC: 94498 AN: 152132 Hom.: 29799 Cov.: 33 AF XY: 0.619 AC XY: 46079 AN XY: 74396

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: 0.652 Hom.: 50869

Bravo AF: 0.621

Asia WGS AF: 0.722 AC: 2512 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	clinical testing	GeneDx	Jun 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.2
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2516829; hg19: chr2-99773201;