chr2-99161677-GA-G

Position:

• chr2-99161677-GA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_145199.3(LIPT1):​c.-1-270del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0558 in 240,628 control chromosomes in the GnomAD database, including 783 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.064 (577 hom., cov: 30)
  • Exomes 𝑓: 0.044 (206 hom.)
• Consequence: LIPT1 NM_145199.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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]

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 2-99161677-GA-G is Benign according to our data. Variant chr2-99161677-GA-G is described in ClinVar as [Benign]. Clinvar id is 1178173.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPT1	NM_145199.3	c.-1-270del		intron_variant		ENST00000651691.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPT1	ENST00000651691.1	c.-1-270del		intron_variant			NM_145199.3	P1

Frequencies

GnomAD3 genomes AF: 0.0636 AC: 9355 AN: 147002 Hom.: 579 Cov.: 30

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.00112

Gnomad AMR AF: 0.0922

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.0330

Gnomad FIN AF: 0.0246

Gnomad MID AF: 0.0258

Gnomad NFE AF: 0.0155

Gnomad OTH AF: 0.0652

GnomAD4 exome AF: 0.0436 AC: 4077 AN: 93530 Hom.: 206 Cov.: 0 AF XY: 0.0424 AC XY: 2083 AN XY: 49134

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.101

Gnomad4 ASJ exome AF: 0.0224

Gnomad4 EAS exome AF: 0.221

Gnomad4 SAS exome AF: 0.0294

Gnomad4 FIN exome AF: 0.0310

Gnomad4 NFE exome AF: 0.0209

Gnomad4 OTH exome AF: 0.0444

GnomAD4 genome AF: 0.0636 AC: 9361 AN: 147098 Hom.: 577 Cov.: 30 AF XY: 0.0641 AC XY: 4587 AN XY: 71574

Gnomad4 AFR AF: 0.132

Gnomad4 AMR AF: 0.0922

Gnomad4 ASJ AF: 0.0231

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.0327

Gnomad4 FIN AF: 0.0246

Gnomad4 NFE AF: 0.0155

Gnomad4 OTH AF: 0.0650

Alfa AF: 0.00750 Hom.: 4

Bravo AF: 0.0717

Asia WGS AF: 0.102 AC: 352 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

Oct 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs140517012; hg19: chr2-99778140;