2-99155118-C-T

Position:

• chr2-99155118-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001204830.2(LIPT1):​c.-378C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00562 in 450,498 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (37 hom., cov: 34)
  • Exomes 𝑓: 0.0019 (8 hom.)
• Consequence: LIPT1 NM_001204830.2 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.932

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]

ENSG00000273155 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 2-99155118-C-T is Benign according to our data. Variant chr2-99155118-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1196049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0128 (1954/152326) while in subpopulation AFR AF= 0.043 (1787/41582). AF 95% confidence interval is 0.0413. There are 37 homozygotes in gnomad4. There are 929 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPT1	NM_145199.3	c.-2+67C>T		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+67C>T		intron_variant			NM_145199.3	ENSP00000498546.1
ENSG00000273155	ENST00000410042.1	c.-154+67C>T		intron_variant		2		ENSP00000387111.1
ENSG00000241962	ENST00000424491.5	n.63+4599C>T		intron_variant		2		ENSP00000390891.1

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1955 AN: 152208 Hom.: 37 Cov.: 34

Gnomad AFR AF: 0.0431

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00667

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000632

Gnomad OTH AF: 0.00812

GnomAD4 exome AF: 0.00194 AC: 579 AN: 298172 Hom.: 8 Cov.: 0 AF XY: 0.00153 AC XY: 260 AN XY: 169784

Gnomad4 AFR exome AF: 0.0433

Gnomad4 AMR exome AF: 0.00277

Gnomad4 ASJ exome AF: 0.000190

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000135

Gnomad4 FIN exome AF: 0.000164

Gnomad4 NFE exome AF: 0.000384

Gnomad4 OTH exome AF: 0.00403

GnomAD4 genome AF: 0.0128 AC: 1954 AN: 152326 Hom.: 37 Cov.: 34 AF XY: 0.0125 AC XY: 929 AN XY: 74488

Gnomad4 AFR AF: 0.0430

Gnomad4 AMR AF: 0.00666

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000632

Gnomad4 OTH AF: 0.00803

Alfa AF: 0.000709 Hom.: 0

Bravo AF: 0.0149

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely 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	-0.88
CADD	Benign	2.2
DANN	Benign	0.84

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: rs56824332; hg19: chr2-99771581;