NM_000098.3:c.1578T>C

Variant names:

• chr1-53211252-T-C
• rs113493395
• NM_000098.3:c.1578T>C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_000098.3(CPT2):​c.1578T>C​(p.Gly526Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00398 in 1,612,504 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0043 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0039 (36 hom.)
• Consequence: CPT2 NM_000098.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: -2.08
• 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: ClinGen, Myriad Women’s Health
• carnitine palmitoyl transferase II deficiency, myopathic form

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia
• carnitine palmitoyl transferase II deficiency, neonatal form

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

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

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

ENSG00000236723 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-53211252-T-C is Benign according to our data. Variant chr1-53211252-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 297609.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.08 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 AR,Unknown gene

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.1578T>C	p.Gly526Gly	synonymous	Exon 4 of 5	NP_000089.1
	CPT2	NM_001330589.2		c.1576+2T>C		splice_donor intron	N/A	NP_001317518.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPT2	ENST00000371486.4	TSL:1 MANE Select	c.1578T>C	p.Gly526Gly	synonymous	Exon 4 of 5	ENSP00000360541.3
	CPT2	ENST00000873097.1		c.1578T>C	p.Gly526Gly	synonymous	Exon 4 of 6	ENSP00000543156.1
	CPT2	ENST00000637252.1	TSL:5	c.1578T>C	p.Gly526Gly	synonymous	Exon 4 of 6	ENSP00000490492.1

Frequencies

GnomAD3 genomes AF: 0.00432 AC: 658 AN: 152140 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0275

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00422

Gnomad OTH AF: 0.00240

GnomAD2 exomes AF: 0.00422 AC: 1044 AN: 247360 AF XY: 0.00411

Gnomad AFR exome AF: 0.00101

Gnomad AMR exome AF: 0.000525

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0248

Gnomad NFE exome AF: 0.00404

Gnomad OTH exome AF: 0.00314

GnomAD4 exome AF: 0.00394 AC: 5756 AN: 1460246 Hom.: 36 Cov.: 34 AF XY: 0.00379 AC XY: 2749 AN XY: 726244

African (AFR) AF: 0.000688 AC: 23 AN: 33442

American (AMR) AF: 0.000561 AC: 25 AN: 44552

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.000280 AC: 24 AN: 85852

European-Finnish (FIN) AF: 0.0250 AC: 1331 AN: 53320

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00367 AC: 4080 AN: 1111262

Other (OTH) AF: 0.00444 AC: 268 AN: 60326

GnomAD4 genome AF: 0.00432 AC: 658 AN: 152258 Hom.: 4 Cov.: 32 AF XY: 0.00545 AC XY: 406 AN XY: 74446

African (AFR) AF: 0.000698 AC: 29 AN: 41556

American (AMR) AF: 0.00274 AC: 42 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.0275 AC: 292 AN: 10608

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

European-Non Finnish (NFE) AF: 0.00422 AC: 287 AN: 68016

Other (OTH) AF: 0.00237 AC: 5 AN: 2106

Alfa AF: 0.00301 Hom.: 1

Bravo AF: 0.00223

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00389 AC: 15

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00489 AC: 42

ExAC AF: 0.00392 AC: 476

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	3	Carnitine palmitoyltransferase II deficiency (3)
-	-	2	not specified (2)
-	-	1	Carnitine palmitoyl transferase II deficiency, myopathic form (1)
-	-	1	Carnitine palmitoyl transferase II deficiency, myopathic form;C1833511:Carnitine palmitoyl transferase II deficiency, severe infantile form;C1833518:Carnitine palmitoyl transferase II deficiency, neonatal form;C3280160:Encephalopathy, acute, infection-induced, susceptibility to, 4 (1)
-	-	1	Carnitine palmitoyl transferase II deficiency, neonatal form (1)
-	-	1	Carnitine palmitoyl transferase II deficiency, severe infantile form (1)
-	-	1	Encephalopathy, acute, infection-induced, susceptibility to, 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.72
DANN	Benign	0.49
FATHMM_MKL	Benign	0.048	N
PhyloP100		-2.1
GERP RS		-5.6
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs113493395; hg19: chr1-53676924;