chr1-53196958-G-A

Variant names:

• chr1-53196958-G-A
• rs1443908294
• NM_000098.3:c.15G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_000098.3(CPT2):​c.15G>A​(p.Leu5Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000289 in 1,386,100 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 (★). Synonymous variant affecting the same amino acid position (i.e. L5L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: CPT2 NM_000098.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.676
• Publications: 0 publications found

Genes affected

CPT2 (HGNC:2330): (carnitine palmitoyltransferase 2) The protein encoded by this gene is a nuclear protein which is transported to the mitochondrial inner membrane. Together with carnitine palmitoyltransferase I, the encoded protein oxidizes long-chain fatty acids in the mitochondria. Defects in this gene are associated with mitochondrial long-chain fatty-acid (LCFA) oxidation disorders. [provided by RefSeq, Jul 2008]

CPT2 Gene-Disease associations (from GenCC):

• carnitine palmitoyltransferase II deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health, ClinGen
• carnitine palmitoyl transferase II deficiency, neonatal form

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• carnitine palmitoyl transferase II deficiency, myopathic form

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• carnitine palmitoyl transferase II deficiency, severe infantile form

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• encephalopathy, acute, infection-induced, susceptibility to, 4

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 1-53196958-G-A is Benign according to our data. Variant chr1-53196958-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2017765.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.676 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000098.3. 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
	CPT2	NM_000098.3	MANE Select	c.15G>A	p.Leu5Leu	synonymous	Exon 1 of 5	NP_000089.1	P23786
	CPT2	NM_001330589.2		c.15G>A	p.Leu5Leu	synonymous	Exon 1 of 5	NP_001317518.1	A0A1B0GTB8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPT2	ENST00000371486.4	TSL:1 MANE Select	c.15G>A	p.Leu5Leu	synonymous	Exon 1 of 5	ENSP00000360541.3	P23786
	CPT2	ENST00000873097.1		c.15G>A	p.Leu5Leu	synonymous	Exon 1 of 6	ENSP00000543156.1
	CPT2	ENST00000637252.1	TSL:5	c.15G>A	p.Leu5Leu	synonymous	Exon 1 of 6	ENSP00000490492.1	A0A1B0GVF3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 135248 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000289 AC: 4 AN: 1386100 Hom.: 0 Cov.: 30 AF XY: 0.00000292 AC XY: 2 AN XY: 685628

African (AFR) AF: 0.00 AC: 0 AN: 29536

American (AMR) AF: 0.00 AC: 0 AN: 38036

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24786

East Asian (EAS) AF: 0.00 AC: 0 AN: 34682

South Asian (SAS) AF: 0.00 AC: 0 AN: 78990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35634

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4326

European-Non Finnish (NFE) AF: 0.00000369 AC: 4 AN: 1082564

Other (OTH) AF: 0.00 AC: 0 AN: 57546

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Carnitine palmitoyltransferase II deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	11
DANN	Benign	0.94
PhyloP100		0.68
PromoterAI		-0.17	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
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: rs1443908294; hg19: chr1-53662630;