NM_145199.3:c.315A>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_145199.3(LIPT1):c.315A>G(p.Thr105Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0312 in 1,612,940 control chromosomes in the GnomAD database, including 2,410 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.062 ( 575 hom., cov: 31)

Exomes 𝑓: 0.028 ( 1835 hom. )

Consequence

LIPT1
NM_145199.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.37

Variant links:

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]

LIPT1 links:

ENSG00000273155 (HGNC:):

ENSG00000273155 links:

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]

MITD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 2-99162272-A-G is Benign according to our data. Variant chr2-99162272-A-G is described in ClinVar as [Benign]. Clinvar id is 380548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-99162272-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.37 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPT1	NM_145199.3 link	c.315A>G	p.Thr105Thr	synonymous_variant	Exon 2 of 2	ENST00000651691.1	NP_660200.1	Q9Y234

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LIPT1	ENST00000651691.1 link	c.315A>G	p.Thr105Thr	synonymous_variant	Exon 2 of 2		NM_145199.3	ENSP00000498546.1	Q9Y234
ENSG00000273155	ENST00000410042.1 link	c.-28+5846A>G		intron_variant	Intron 2 of 5	2		ENSP00000387111.1
ENSG00000241962	ENST00000424491.5 link	n.63+11753A>G		intron_variant	Intron 4 of 13	2		ENSP00000390891.1

Frequencies

GnomAD3 genomes

AF:

0.0620

AC:

9428

AN:

152150

Hom.:

577

Cov.:

show subpopulations

Gnomad AFR

AF:

0.130

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0895

Gnomad ASJ

AF:

0.0228

Gnomad EAS

AF:

0.204

Gnomad SAS

AF:

0.0323

Gnomad FIN

AF:

0.0217

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0151

Gnomad OTH

AF:

0.0626

GnomAD3 exomes

AF:

0.0532

AC:

13262

AN:

249484

Hom.:

788

AF XY:

0.0468

AC XY:

6312

AN XY:

135004

show subpopulations

Gnomad AFR exome

AF:

0.133

Gnomad AMR exome

AF:

0.114

Gnomad ASJ exome

AF:

0.0189

Gnomad EAS exome

AF:

0.201

Gnomad SAS exome

AF:

0.0255

Gnomad FIN exome

AF:

0.0209

Gnomad NFE exome

AF:

0.0161

Gnomad OTH exome

AF:

0.0420

GnomAD4 exome

AF:

0.0280

AC:

40859

AN:

1460670

Hom.:

1835

Cov.:

AF XY:

0.0271

AC XY:

19727

AN XY:

726706

show subpopulations

Gnomad4 AFR exome

AF:

0.129

Gnomad4 AMR exome

AF:

0.109

Gnomad4 ASJ exome

AF:

0.0202

Gnomad4 EAS exome

AF:

0.224

Gnomad4 SAS exome

AF:

0.0255

Gnomad4 FIN exome

AF:

0.0214

Gnomad4 NFE exome

AF:

0.0148

Gnomad4 OTH exome

AF:

0.0379

GnomAD4 genome

AF:

0.0620

AC:

9434

AN:

152270

Hom.:

575

Cov.:

AF XY:

0.0621

AC XY:

4623

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.129

Gnomad4 AMR

AF:

0.0895

Gnomad4 ASJ

AF:

0.0228

Gnomad4 EAS

AF:

0.204

Gnomad4 SAS

AF:

0.0319

Gnomad4 FIN

AF:

0.0217

Gnomad4 NFE

AF:

0.0151

Gnomad4 OTH

AF:

0.0624

Alfa

AF:

0.0298

Hom.:

221

Bravo

AF:

0.0717

Asia WGS

AF:

0.0960

AC:

334

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Dec 22, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.24

DANN

Benign

0.57

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over