2-99161677-GA-GAA

Variant names:

• chr2-99161677-G-GA
• rs140517012
• NM_145199.3:c.-1-270dupA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_145199.3(LIPT1):​c.-1-270dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0062 in 239,398 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 30)
  • Exomes 𝑓: 0.016 (0 hom.)
• Consequence: LIPT1 NM_145199.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46

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:):

MITD1 (HGNC:25207): (microtubule interacting and trafficking domain containing 1) Abscission, the separation of daughter cells at the end of cytokinesis, is effected by endosomal sorting complexes required for transport III (ESCRT-III). The protein encoded by this gene functions as a homodimer, with the N-termini binding to a subset of ESCRT-III subunits and the C-termini binding to membranes. The encoded protein regulates ESCRT-III activity and is required for proper cytokinesis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0158 (1457/92368) while in subpopulation NFE AF= 0.0174 (1028/59192). AF 95% confidence interval is 0.0165. There are 0 homozygotes in gnomad4_exome. There are 756 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPT1	NM_145199.3	c.-1-270dupA		intron_variant	Intron 1 of 1	ENST00000651691.1	NP_660200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPT1	ENST00000651691.1	c.-1-280_-1-279insA		intron_variant	Intron 1 of 1		NM_145199.3	ENSP00000498546.1
ENSG00000273155	ENST00000410042.1	c.-28+5251_-28+5252insA		intron_variant	Intron 2 of 5	2		ENSP00000387111.1
ENSG00000241962	ENST00000424491.5	n.63+11158_63+11159insA		intron_variant	Intron 4 of 13	2		ENSP00000390891.1

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 27 AN: 147030 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000348

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000196

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0158 AC: 1457 AN: 92368 Hom.: 0 Cov.: 0 AF XY: 0.0156 AC XY: 756 AN XY: 48538

Gnomad4 AFR exome AF: 0.0123

Gnomad4 AMR exome AF: 0.00898

Gnomad4 ASJ exome AF: 0.0176

Gnomad4 EAS exome AF: 0.00875

Gnomad4 SAS exome AF: 0.0127

Gnomad4 FIN exome AF: 0.0166

Gnomad4 NFE exome AF: 0.0174

Gnomad4 OTH exome AF: 0.0162

GnomAD4 genome AF: 0.000184 AC: 27 AN: 147030 Hom.: 0 Cov.: 30 AF XY: 0.000196 AC XY: 14 AN XY: 71486

Gnomad4 AFR AF: 0.000348

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000196

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs140517012; hg19: chr2-99778140;