2-99162014-C-T

Variant names:

• chr2-99162014-C-T
• rs150251923
• NM_145199.3:c.57C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_145199.3(LIPT1):​c.57C>T​(p.Val19Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000075 in 1,613,538 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000077 (0 hom.)
• Consequence: LIPT1 NM_145199.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.806
• Publications: 0 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 2-99162014-C-T is Benign according to our data. Variant chr2-99162014-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 719168.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.806 with no splicing effect.

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.57C>T	p.Val19Val	synonymous	Exon 2 of 2	NP_660200.1	Q9Y234
	LIPT1	NM_001204830.2		c.57C>T	p.Val19Val	synonymous	Exon 3 of 3	NP_001191759.1	Q9Y234
	LIPT1	NM_015929.4		c.57C>T	p.Val19Val	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.57C>T	p.Val19Val	synonymous	Exon 2 of 2	ENSP00000498546.1	Q9Y234
	LIPT1	ENST00000393473.6	TSL:1	c.57C>T	p.Val19Val	synonymous	Exon 3 of 3	ENSP00000377115.2	Q9Y234
	ENSG00000273155	ENST00000410042.1	TSL:2	c.-28+5588C>T		intron	N/A	ENSP00000387111.1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152082 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000359 AC: 9 AN: 250664 AF XY: 0.0000295

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000490

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000766 AC: 112 AN: 1461338 Hom.: 0 Cov.: 31 AF XY: 0.0000702 AC XY: 51 AN XY: 726950

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00247 AC: 98 AN: 39684

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86202

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111606

Other (OTH) AF: 0.0000166 AC: 1 AN: 60366

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152200 Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4 AN XY: 74412

African (AFR) AF: 0.00 AC: 0 AN: 41536

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67996

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000264

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	1.3
DANN	Benign	0.51
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs150251923; hg19: chr2-99778477;