2-99162272-A-G

Variant names:

• chr2-99162272-A-G
• rs3791211
• NM_145199.3:c.315A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.37
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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 VariationId is 380548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145199.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPT1	NM_145199.3	MANE Select	c.315A>G	p.Thr105Thr	synonymous	Exon 2 of 2	NP_660200.1	Q9Y234
	LIPT1	NM_001204830.2		c.315A>G	p.Thr105Thr	synonymous	Exon 3 of 3	NP_001191759.1	Q9Y234
	LIPT1	NM_015929.4		c.315A>G	p.Thr105Thr	synonymous	Exon 3 of 3	NP_057013.1	Q9Y234

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPT1	ENST00000651691.1	MANE Select	c.315A>G	p.Thr105Thr	synonymous	Exon 2 of 2	ENSP00000498546.1	Q9Y234
	LIPT1	ENST00000393473.6	TSL:1	c.315A>G	p.Thr105Thr	synonymous	Exon 3 of 3	ENSP00000377115.2	Q9Y234
	ENSG00000273155	ENST00000410042.1	TSL:2	c.-28+5846A>G		intron	N/A	ENSP00000387111.1

Frequencies

GnomAD3 genomes AF: 0.0620 AC: 9428 AN: 152150 Hom.: 577 Cov.: 31

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

GnomAD2 exomes AF: 0.0532 AC: 13262 AN: 249484 AF XY: 0.0468

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 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.: 32 AF XY: 0.0271 AC XY: 19727 AN XY: 726706

African (AFR) AF: 0.129 AC: 4306 AN: 33476

American (AMR) AF: 0.109 AC: 4887 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 527 AN: 26132

East Asian (EAS) AF: 0.224 AC: 8909 AN: 39696

South Asian (SAS) AF: 0.0255 AC: 2203 AN: 86252

European-Finnish (FIN) AF: 0.0214 AC: 1122 AN: 52456

Middle Eastern (MID) AF: 0.0272 AC: 157 AN: 5766

European-Non Finnish (NFE) AF: 0.0148 AC: 16462 AN: 1111788

Other (OTH) AF: 0.0379 AC: 2286 AN: 60380

GnomAD4 genome AF: 0.0620 AC: 9434 AN: 152270 Hom.: 575 Cov.: 31 AF XY: 0.0621 AC XY: 4623 AN XY: 74466

African (AFR) AF: 0.129 AC: 5377 AN: 41522

American (AMR) AF: 0.0895 AC: 1370 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0228 AC: 79 AN: 3470

East Asian (EAS) AF: 0.204 AC: 1055 AN: 5176

South Asian (SAS) AF: 0.0319 AC: 154 AN: 4826

European-Finnish (FIN) AF: 0.0217 AC: 231 AN: 10622

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0151 AC: 1027 AN: 68032

Other (OTH) AF: 0.0624 AC: 132 AN: 2114

Alfa AF: 0.0327 Hom.: 633

Bravo AF: 0.0717

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.24
DANN	Benign	0.57
PhyloP100		-1.4
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3791211; hg19: chr2-99778735; COSMIC: COSV60740171; COSMIC: COSV60740171;