NM_152246.3:c.2263C>A

Variant names:

• chr22-50569394-G-T
• NM_152246.3:c.2263C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_152246.3(CPT1B):​c.2263C>A​(p.Arg755Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CPT1B NM_152246.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.30
• Publications: 0 publications found

Genes affected

CPT1B (HGNC:2329): (carnitine palmitoyltransferase 1B) The protein encoded by this gene, a member of the carnitine/choline acetyltransferase family, is the rate-controlling enzyme of the long-chain fatty acid beta-oxidation pathway in muscle mitochondria. This enzyme is required for the net transport of long-chain fatty acyl-CoAs from the cytoplasm into the mitochondria. Multiple transcript variants encoding different isoforms have been found for this gene, and read-through transcripts are expressed from the upstream locus that include exons from this gene. [provided by RefSeq, Jun 2009]

CHKB-CPT1B (HGNC:41998): (CHKB-CPT1B readthrough (NMD candidate)) The genes CHKB and CPT1B are adjacent on chromosome 22 and read-through transcripts are expressed that include exons from both loci. The read-through transcripts are candidates for nonsense-mediated mRNA decay (NMD) and are unlikely to express proteins. [provided by RefSeq, Jun 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPT1B	NM_152246.3	c.2263C>A	p.Arg755Ser	missense_variant	Exon 19 of 20	ENST00000312108.12	NP_689452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPT1B	ENST00000312108.12	c.2263C>A	p.Arg755Ser	missense_variant	Exon 19 of 20	1	NM_152246.3	ENSP00000312189.8
CHKB-CPT1B	ENST00000453634.5	n.*2488C>A		non_coding_transcript_exon_variant	Exon 22 of 23	5		ENSP00000457031.1
CHKB-CPT1B	ENST00000453634.5	n.*2488C>A		3_prime_UTR_variant	Exon 22 of 23	5		ENSP00000457031.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 06, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2263C>A (p.R755S) alteration is located in exon 19 (coding exon 18) of the CPT1B gene. This alteration results from a C to A substitution at nucleotide position 2263, causing the arginine (R) at amino acid position 755 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.48	T;T;T;T;.
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.0098
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.88	.;.;.;D;D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.47	T;T;T;T;T
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Benign	1.3	L;L;L;L;.
PhyloP100		1.3
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.3	N;N;N;N;N
REVEL	Uncertain	0.35
Sift	Benign	0.37	T;T;T;T;T
Sift4G	Benign	0.65	T;T;T;T;T
Polyphen		0.050	B;B;B;B;.
Vest4		0.45
MutPred		0.63		Loss of MoRF binding (P = 0.0775);Loss of MoRF binding (P = 0.0775);Loss of MoRF binding (P = 0.0775);Loss of MoRF binding (P = 0.0775);.;
MVP		0.87
ClinPred		0.69	D
GERP RS		5.1
Varity_R		0.28
gMVP		0.56
Mutation Taster		=80/20	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

hg19: chr22-51007823;