2-99155036-C-T

Position:

• chr2-99155036-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_145199.3(LIPT1):​c.-17C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 455,812 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (5 hom., cov: 34)
  • Exomes 𝑓: 0.00052 (0 hom.)
• Consequence: LIPT1 NM_145199.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0720

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-99155036-C-T is Benign according to our data. Variant chr2-99155036-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 382788.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00393 (599/152342) while in subpopulation AFR AF= 0.0138 (573/41580). AF 95% confidence interval is 0.0128. There are 5 homozygotes in gnomad4. There are 304 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPT1	NM_145199.3	c.-17C>T		5_prime_UTR_premature_start_codon_gain_variant	1/2	ENST00000651691.1	NP_660200.1
LIPT1	NM_145199.3	c.-17C>T		5_prime_UTR_variant	1/2	ENST00000651691.1	NP_660200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPT1	ENST00000651691	c.-17C>T		5_prime_UTR_premature_start_codon_gain_variant	1/2		NM_145199.3	ENSP00000498546.1
ENSG00000273155	ENST00000410042	c.-169C>T		5_prime_UTR_premature_start_codon_gain_variant	1/6	2		ENSP00000387111.1
LIPT1	ENST00000651691	c.-17C>T		5_prime_UTR_variant	1/2		NM_145199.3	ENSP00000498546.1
ENSG00000273155	ENST00000410042	c.-169C>T		5_prime_UTR_variant	1/6	2		ENSP00000387111.1
ENSG00000241962	ENST00000424491.5	n.63+4517C>T		intron_variant		2		ENSP00000390891.1

Frequencies

GnomAD3 genomes AF: 0.00391 AC: 595 AN: 152224 Hom.: 5 Cov.: 34

Gnomad AFR AF: 0.0137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.000901 AC: 117 AN: 129880 Hom.: 0 AF XY: 0.000733 AC XY: 52 AN XY: 70944

Gnomad AFR exome AF: 0.0149

Gnomad AMR exome AF: 0.000698

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000179

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000407

Gnomad OTH exome AF: 0.000750

GnomAD4 exome AF: 0.000521 AC: 158 AN: 303470 Hom.: 0 Cov.: 0 AF XY: 0.000417 AC XY: 72 AN XY: 172816

Gnomad4 AFR exome AF: 0.0137

Gnomad4 AMR exome AF: 0.000807

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.000493

GnomAD4 genome AF: 0.00393 AC: 599 AN: 152342 Hom.: 5 Cov.: 34 AF XY: 0.00408 AC XY: 304 AN XY: 74484

Gnomad4 AFR AF: 0.0138

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00171 Hom.: 1

Bravo AF: 0.00435

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	15
DANN	Benign	0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs181470779; hg19: chr2-99771499;